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"Oncol Rep"[jour]
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1.
Oncol Rep. 2020 Jan 31. doi: 10.3892/or.2020.7485. [Epub ahead of print]
Periostin induces epithelial‑to‑mesenchymal transition via the integrin α5β1/TWIST‑2 axis in cholangiocarcinoma.
Sonongbua J1, Siritungyong S1, Thongchot S2, Kamolhan T2, Utispan K3, Thuwajit P2, Pongpaibul A4, Wongkham S5, Thuwajit C2.
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Abstract
Periostin (PN) (also known as osteoblast‑specific factor OSF‑2) is a protein that in humans is encoded by the POSTN gene and has been correlated with a reduced survival of cholangiocarcinoma (CCA) patients, with the well‑known effect of inducing epithelial‑to‑mesenchymal transition (EMT). The present study investigated the effect of PN, through integrin (ITG)α5β1, in EMT‑mediated CCA aggressiveness. The alterations in EMT‑related gene and protein expression were investigated by real‑time PCR, western blot analysis and zymogram. The effects of PN on migration and the level of TWIST‑2 were assessed in CCA cells with and without siITGα5 transfection. PN was found to induce CCA cell migration and EMT features, including increments in Twist‑related protein 2 (TWIST‑2), zinc finger protein SNAI1 (SNAIL‑1), α-smooth muscle actin (ASMA), vimentin (VIM) and matrix metallopeptidase 9 (MMP‑9), and a reduction in cytokeratin 19 (CK‑19) together with cytoplasmic translocation of E-cadherin (CDH‑1). Additionally, PN markedly induced MMP‑9 activity. TWIST‑2 was significantly induced in PN‑treated CCA cells; this effect was attenuated in the ITGα5β1‑knockdown cells and corresponded to reduced migration of the cancer cells. These results indicated that PN induced CCA migration through ITGα5β1/TWIST-2‑mediated EMT. Moreover, clinical samples from CCA patients showed that higher levels of TWIST‑2 were significantly correlated with shorter survival time. In conclusion, the ITGα5β1‑mediated TWIST‑2 signaling pathway regulates PN‑induced EMT in CCA progression, and TWIST‑2 is a prognostic marker of poor survival in CCA patients.
PMID: 32020235 DOI: 10.3892/or.2020.7485
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Select item 320202342.
Oncol Rep. 2020 Jan 14. doi: 10.3892/or.2020.7462. [Epub ahead of print]
Identification of anaplastic lymphoma kinase fusions in clear cell renal cell carcinoma.
Chen W1, Li W2, Bai B3, Wei H4.
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Abstract
As one of the most common types of renal cancer, clear cell renal cell carcinoma (ccRCC) in advanced stages constitutes a continued major challenge for uro‑oncologists, as the identification of novel driver mutations and the development of novel targeted therapies against them remain an unmet need. Aberrations in anaplastic lymphoma kinase (ALK), a rational therapeutic target, as verified in lung cancer with ALK rearrangement, have been implicated in the pathogenesis of multiple human cancers. In the present study, we screened ALK expression in 87 pathologically defined ccRCCs via immunohistochemistry (IHC) using a newly developed rabbit anti‑human ALK monoclonal antibody (clone D5F3). Four patients tested positive for ALK expression, as confirmed by IHC. Among them, 2 patients were further confirmed with fluorescence in situ hybridization (FISH) assay with the use of the Vysis LSI ALK dual color break‑apart probe. Furthermore, we detected the existence of the echinoderm microtubule‑associated protein‑like 4/anaplastic lymphoma kinase (EML4‑ALK) (E13:A20, variant 1) fusion gene in tumors from these two patients by using rapid amplification of cDNA ends (RACE)‑coupled PCR sequencing and RT‑PCR. Notably, we first showed that enforced EML4‑ALK expression could significantly promote in vitro proliferation, clonogenic colony formation and apoptosis resistance in HK2 immortalized normal renal tubal epithelial cells and their in vivo outgrowth when injected into immunocompromised nude mice. Importantly, this pro‑tumorigenic effect was completely abolished by the ALK‑specific inhibitor crizotinib, indicating the potential effectiveness of ALK‑specific inhibitors in treating ALK‑rearranged ccRCC patients. Our data revealed that ALK fusions exist in adult ccRCC, providing a rationale for ALK inhibitor therapy in selected patients with ccRCC.
PMID: 32020234 DOI: 10.3892/or.2020.7462
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Select item 320202333.
Oncol Rep. 2020 Jan 14. doi: 10.3892/or.2020.7463. [Epub ahead of print]
Treatment with a probiotic combination reduces abdominal adhesion in rats by decreasing intestinal inflammation and restoring microbial composition.
Deng X1, Zheng C1, Wang S1, Yang R1, Liu Z2, Chen T1.
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Abstract
Abdominal adhesions refer to abnormal adhesions which cause a series of complications in numerous patients. In the present study, the beneficial effect of a combination of probiotics (Lactobacillus plantarum, L. acidophilus, L. rhamnosus and Bifidobacterium animalis) on abdominal adhesions in a rat model were verified. The present results indicated that probiotic treatment significantly reduced the levels of proinflammatory factors interleukin (IL)‑1β, IL‑6 and TNF‑α in serum and intestinal tissue (P<0.05), and markedly downregulated the inflammatory (TLR4/NF‑κB) and fibrotic (TGF‑β1/Smad) signalling pathways in intestinal tissue, especially in the prevention group (P<0.01). The high‑throughput sequencing results further supported that the probiotics significantly increased the relative abundance of probiotic Bacteroidetes (at the phylum level), Bacteroidales (at the order level), Lactobacillales (at the order level) and Lactobacillus (at the genus level), and markedly reduced the number of pathogenic Proteobacteria (at the phylum level), Erysipelotrichales (at the order level), Verrucomicrobiales (at the order level), Klebsiella (at the genus level) and Serratia (at the genus level). In conclusion, probiotics can effectively reduce abdominal adhesions by restoring the microbial balance and reducing inflammation and fibrosis caused by surgery.
PMID: 32020233 DOI: 10.3892/or.2020.7463
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Select item 320202324.
Oncol Rep. 2020 Jan 23. doi: 10.3892/or.2020.7477. [Epub ahead of print]
High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia.
Ma P1, Xing M2, Han L1, Gan S1, Ma J1, Wu F1, Huang Y1, Chen Y1, Tian W1, An C1, Sun H1, Sun L1.
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Abstract
Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD‑L1) regulates tumor cells glycolysis using real time PCR (RT‑PCR), western blotting and flow cytometry. PD‑L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD‑L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis‑associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD‑L1 high‑expressed cell line. Overexpressed PD‑L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD‑L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD‑L1‑overexpressed cell line (PD‑L1‑OV) MOLM‑13 exhibited rapid tumor progression. Glycolysis‑associated genes were highly expressed in tumor tissues of PD‑L1‑OV MOLM‑13, with increased Ki67. Based on these findings, PD‑L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.
PMID: 32020232 DOI: 10.3892/or.2020.7477
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Select item 320202315.
Oncol Rep. 2020 Jan 23. doi: 10.3892/or.2020.7478. [Epub ahead of print]
Knockdown of SLCO4C1 inhibits cell proliferation and metastasis in endometrial cancer through inactivating the PI3K/Akt signaling pathway.
Hu X1, Han T1, Bian Y1, Tong H1, Wen X1, Li Y1, Wan X1.
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Abstract
Endometrial cancer (EC) is the second leading type of cancer among women, and its progression is dependent on several factors. The aim of the present study was to examine the effect of solute carrier organic anion transporter family member 4C1 (SLCO4C1) on human EC and determine the underlying molecular mechanism. A total of 57 differentially expressed genes associated with advanced stage and survival were identified in The Cancer Genome Atlas database. In addition, gene ontology analysis indicated that SLCO4C1 was highly expressed in cell differentiation and integral component of plasma membrane. High SLCO4C1 expression in EC tissues was verified by immunohistochemistry. The results demonstrated that the downregulation of SLCO4C1 could significantly suppress the viability, sphere formation, migration and invasion abilities of cells, but enhance apoptosis in EC cell lines. Furthermore, the present results demonstrated that SLCO4C1 had effects on the epithelial‑mesenchymal transition (EMT) phenotype in EC cells and regulated the expression of EMT‑related proteins. Mechanistically, the present study revealed that SLCO4C1 regulated the biological functions of EC cells by inactivating the PI3K/Akt signaling pathway. Collectively, it was demonstrated that the SLCO4C1/PI3K/Akt pathway may play an important role in EC progression and metastasis and serve as a potential biomarker and target for EC diagnosis and treatment.
PMID: 32020231 DOI: 10.3892/or.2020.7478
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Select item 320202306.
Oncol Rep. 2020 Jan 23. doi: 10.3892/or.2020.7479. [Epub ahead of print]
Myoglobin variants are expressed in human glioblastoma cells‑hypoxia effect?
El-Tohamy R1, Elkholi I1, Elsherbiny ME2, Magdy M3, Hammam O3, Allalunis-Turner J4, Emara M1.
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Abstract
Glioblastoma multiforme (GBM) is the most aggressive human brain cancer. Little is known regarding how these cells adapt to the harsh tumor microenvironment, and consequently survive and resist various treatments. Myoglobin (MB), the oxygen‑binding hemoprotein, has been shown to be ectopically expressed in different human cancers and cell lines, and its expression is hypothesized to be an adaptation mechanism to hypoxia. The aim of the present study was to determine whether cancer‑related and hypoxia‑responsive MB mRNA splice variants are expressed in human GBM cells and glioblastoma tumor xenografts, and whether their expression is induced by hypoxia and correlated with hypoxia markers [lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CAIX)]. Conventional reverse transcription (RT)‑PCR, DNA sequencing, RT‑quantitative PCR and immunohistochemistry were conducted to investigate MB expression in hypoxia‑sensitive (M010b, M059J) and ‑tolerant (M059K, M006xLo) GBM cell lines that also exhibit differential response towards radiation, rendering them a valuable translational GBM model. It was revealed that cancer‑related MB variants 9, 10, 11 and 13 were expressed in GBM cells under normoxia, and following hypoxia, their expression exhibited modest‑to‑significant upregulation that correlated with hypoxia markers. It was also demonstrated that MB was upregulated in hypoxic microregions of glioblastoma tumor xenografts that were stained in matched tumor regions of serial tumor sections with the hypoxia markers, pimonidazole, CAIX, VEGF and LDHA. The present study identified myoglobin as a potential contributor to the hypoxia adaptation and survival strategies of glioblastoma, and may explain the aggressiveness and frequent recurrence rates associated with GBM.
PMID: 32020230 DOI: 10.3892/or.2020.7479
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Select item 320202297.
Oncol Rep. 2020 Jan 14. doi: 10.3892/or.2020.7465. [Epub ahead of print]
Cyclin F is involved in response to cisplatin treatment in melanoma cell lines.
Krajewski A1, Gagat M1, Żuryń A1, Hałas-Wiśniewska M1, Grzanka D2, Grzanka A1.
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Abstract
Cyclin F is a non‑canonical cyclin which is a part of the SKP1‑CUL1‑F‑box protein (SCF) E3 ubiquitin‑protein ligase complex. Cyclin F is responsible for target recognition, ubiquitination, and degradation of various molecular targets. This protein also controls genome stability through the degradation of ribonucleotide reductase subunit M2 (RRM2). In the present study, the difference between cyclin F expression in cell lines derived from primary and metastatic melanoma, A375 and RPMI‑7951, respectively, were investigated using a western blot analysis and flow cytometry assays. A decrease in cyclin F expression in the A375 cells and an increase in RPMI‑7951 cells after cisplatin treatment were observed. These changes may be related to a mutation in p53 in the RPMI‑7951 cell line. Flow cytometry was conducted to observe that the RPMI‑7951 cell line exhibited greater susceptibility to cisplatin, associated with lack of proper cell cycle control. Therefore, it is possible that cyclin F may modulate drug response in melanoma. The presented data describe cyclin F as a new potential factor that contributes to drug resistance in melanoma patients.
PMID: 32020229 DOI: 10.3892/or.2020.7465
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Select item 320202288.
Oncol Rep. 2020 Jan 29. doi: 10.3892/or.2020.7482. [Epub ahead of print]
Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate.
Piątkowska-Chmiel I1, Gawrońska-Grzywacz M1, Natorska-Chomicka D1, Herbet M1, Sysa M1, Iwan M1, Korga A1, Dudka J1.
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Abstract
Kidney cancer is one of the most lethal urological malignancies associated with a high risk of mortality. Recent studies have shown that several antidiabetic drugs may limit the risk of the growth of different types of cancer. Pioglitazone (PIO) belongs to a novel class of antidiabetic drugs called thiazolidinediones (TZDs), which are commonly used in the treatment of type 2 diabetes. This drug has been demonstrated to exert an inhibitory effect on cell growth in colon, prostatic, breast and pancreatic cancer lines. The aim of the present study was to assess the inhibitory effect of PIO on the proliferation of the renal adenocarcinoma cell line 769‑P. In addition, the proapoptotic potential of combined treatment with PIO and methotrexate (MTX) was evaluated, as well as the impact of the above drugs on the cell cycle of the 769‑P cells. The present study showed that PIO efficaciously inhibited the proliferation and viability of renal cancer cells, and it induced sub‑G1 cell cycle arrest and a decrease in the number of cells in the G2 phase, which indicated cytotoxic activity. PIO also exhibited proapoptotic properties at the lowest dose applied (10 µM). Furthermore, combined therapy with PIO and MTX increased the sensitivity of tumor cells to MTX while at the same time this combined therapy did not exhibit a cytotoxic effect to normal kidney cells. In renal adenocarcinoma cells, the combination of the above cytostatic agent at the lowest dose administered (MTX, 5 µM) with the peroxisome proliferator‑activated receptor γ agonist PIO exhibited better efficacy in triggering the process of apoptosis than that displayed by MTX alone.
PMID: 32020228 DOI: 10.3892/or.2020.7482
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Select item 320202279.
Oncol Rep. 2020 Jan 31. doi: 10.3892/or.2020.7486. [Epub ahead of print]
MicroRNA‑299‑5p inhibits cell metastasis in breast cancer by directly targeting serine/threonine kinase 39.
Li C1, Wang A1, Chen Y1, Liu Y2, Zhang H3, Zhou J4.
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Abstract
Numerous studies have demonstrated that microRNAs (miRNAs) play a key role in human carcinogenesis and metastasis. For example, miR‑299‑5p has previously been revealed to be dysregulated in several human cancers. However, the biological function of miR‑299‑5p in breast cancer remains unclear. The present study demonstrated that miR‑299‑5p was downregulated in breast cancer tissues and cell lines. The restoration of miR‑299‑5p expression suppressed cell migration and invasion, whereas inhibition of miR‑299‑5p promoted cell migration and invasion. In addition, in vivo studies demonstrated that miR‑299‑5p overexpression was able to inhibit tumour metastasis in nude mice. Mechanistically, through bioinformatics analysis and a dual‑luciferase assay, it was confirmed that miR‑299‑5p directly targets serine/threonine kinase 39 (STK39). Silencing STK39 inhibited cell metastasis and suppressed epithelial‑mesenchymal transition markers and matrix metalloproteinase expression, whereas restoration of STK39 expression was able to reverse miR‑299‑5p‑inhibited cell migration and invasion. Collectively, the results of the present study demonstrated that miR‑299‑5p supresses breast cancer cell migration and invasion by targeting STK39. These findings may provide novel insights into miR‑299‑5p and its potential diagnostic and therapeutic benefits in breast cancer.
PMID: 32020227 DOI: 10.3892/or.2020.7486
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Select item 3202022610.
Oncol Rep. 2020 Feb 3. doi: 10.3892/or.2020.7487. [Epub ahead of print]
Tumor necrosis factor‑related apoptosis‑inducing ligand as a therapeutic option in urothelial cancer cells with acquired resistance against first‑line chemotherapy.
Vallo S1, Stege H1, Berg M1, Michaelis M2, Winkelmann R3, Rothweiler F1, Cinatl J Jr1.
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Abstract
Patients with urothelial carcinoma frequently fail to respond to first‑line chemotherapy using cisplatin and gemcitabine due to development of resistant tumor cells. The aim of the present study was to investigate whether an alternative treatment with tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) that induces tumor cell death via the extrinsic apoptotic pathway may be effective against chemotherapy‑resistant urothelial cancer cell lines. The viability of the urothelial cancer cell line RT112 and its chemotherapy‑adapted sublines was investigated by MTT assay. The expression of anti‑apoptotic proteins was determined by western blotting and the individual roles of cellular inhibitor of apoptosis protein (cIAP)1, cIAP2, x‑linked inhibitor of apoptosis protein (XIAP) and induced myeloid leukemia cell differentiation protein (Mcl‑1) were investigated by siRNA‑mediated depletion. In particular, the bladder cancer sublines that were resistant to gemcitabine and cisplatin were cross‑resistant to TRAIL. Resistant cells displayed upregulation of anti‑apoptotic molecules compared with the parental cell line. Treatment with the second mitochondrial activator of caspases (SMAC) mimetic LCL‑161 that antagonizes cIAP1, cIAP2 and XIAP resensitized chemoresistant cells to TRAIL. The resensitization of tumor cells to TRAIL was confirmed by depletion of antiapoptotic proteins with siRNA. Collectively, the findings of the present study demonstrated that SMAC mimetic LCL‑161 increased the sensitivity of the parental cell line RT112 and chemotherapy‑resistant sublines to TRAIL, suggesting that inhibiting anti‑apoptotic molecules renders TRAIL therapy highly effective for chemotherapy‑sensitive and ‑resistant urothelial cancer cells.
PMID: 32020226 DOI: 10.3892/or.2020.7487
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Select item 3202022511.
Oncol Rep. 2020 Jan 27. doi: 10.3892/or.2020.7481. [Epub ahead of print]
Variant analysis of prostate cancer in Japanese patients and a new attempt to predict related biological pathways.
Kasajima R1, Yamaguchi R2, Shimizu E2, Tamada Y2, Niida A3, Tremmel G2, Kishida T4, Aoki I5, Imoto S6, Miyano S2, Uemura H7, Miyagi Y1.
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Abstract
There are regional and/or ethnic differences in tumorigenic pathways among several types of cancer, including prostate cancer (PCa). However, information on genome‑wide gene alterations and the transcriptome is currently only available for PCa patients from Western countries. In order to profile the genetic alterations in Japanese patients with PCa, new panels were created to examine nucleotide sequence variations in 71 selected PCa‑related genes (KCC71) and to detect all fusion RNA transcripts known in PCa (PCaFusion). An analysis of 21 Japanese PCa cases identified 33 different somatic variants in 24 genes in the KCC71 panel, including 2 in SPOP (F102V and F133L), 2 in BRCA2 (I1859fs and R2318ter, resulting in premature termination of the polypeptide), and 1 each in BRAF (K601E), CDH1 (E880K) and RB1 (R621S), as pathogenic alterations. Unexpectedly, the TMPRSS2‑ERG fusion transcript was detected in only 1 case, although the SLC45A3‑ELK4 and USP9Y‑TTTY15 fusion transcripts, known as transcription‑mediated chimeric RNAs, were detected in all examined cases. A new pathway analysis with The Cancer Network Galaxy (TCNG), a cancer gene regulatory network database, was also applied in an attempt to predict molecular pathways implicated in PCa in the Japanese population. Based on the 24 genes having somatic variants identified by the panel analysis as initial seed genes, a putative core network was finally established, including 5 identified genes, namely TNK2, SOX9, CDH1, FOXA1 and TP53, with high commonality from TCNG datasets. These genes are expected to be involved in tumor development, as revealed by the results of an enrichment analysis with Gene Ontology terms. This analysis must be further extended to include more cases in order to verify this method and also to elucidate the characteristics of PCa in Japanese patients.
PMID: 32020225 DOI: 10.3892/or.2020.7481
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Select item 3202022412.
Oncol Rep. 2020 Feb 3. doi: 10.3892/or.2020.7488. [Epub ahead of print]
DEK promotes the proliferation and invasion of lung cancers and indicates poor prognosis in lung adenocarcinomas.
Yang MQ1, Bai LL2, Lei L1, Zheng YW1, Wang Z1, Li ZH1, Liu CC1, Huang WJ1, Xu HT1.
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Abstract
DEK has been revealed to be overexpressed in many cancers and associated with cancer progression. The aim of the present study was to elucidate the role of DEK with a specific focus on its underlying mechanism in lung cancers. DEK expression in lung cancers and normal lung tissues and the correlations between DEK expression and clinicopathological parameters of lung cancers were investigated using the data from The Cancer Genome Atlas (TCGA). DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in A549 and H1299 cells. The effects of DEK on the Wnt signaling pathway and epithelial‑mesenchymal transition (EMT) were examined using western blotting. Proliferative and invasive abilities were observed in A549 and H1299 cells treated with DEK using an MTT assay, colony formation assay, and Transwell migration and invasion assays. The expression of DEK was higher in lung cancer tissues than that in normal lung tissues. DEK expression was positively correlated with the expression of epidermal growth factor receptor (EGFR) and KRAS in lung adenocarcinomas. High expression of DEK indicated poor prognosis in lung adenocarcinomas (P=0.018). Enhanced expression of DEK upregulated the levels of active‑β‑catenin and Wnt target genes, such as cyclin D1, c‑Myc and MMP7 and increased the proliferative and invasive abilities of lung cancer cells. Enhanced expression of DEK in A549 and H1299 cells also increased the levels of EGFR, KRAS, vimentin, Snail, and N‑cadherin, and decreased the level of E‑cadherin. The opposite results were obtained with knockdown of DEK expression. DEK was highly expressed in lung cancers and indicated poor prognosis in lung adenocarcinomas. DEK expression activated the Wnt signaling pathway and EMT process and promoted the proliferation and invasion of lung cancers.
PMID: 32020224 DOI: 10.3892/or.2020.7488
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Select item 3202022313.
Oncol Rep. 2020 Jan 27. doi: 10.3892/or.2020.7480. [Epub ahead of print]
Linc00261 inhibits metastasis and the WNT signaling pathway of pancreatic cancer by regulating a miR‑552‑5p/FOXO3 axis.
Chen T1, Lei S1, Zeng Z1, Zhang J1, Xue Y1, Sun Y1, Lan J1, Xu S2, Mao D3, Guo B4.
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Abstract
The biological function of long non‑coding RNA00261 (Linc00261) has been widely investigated in various types of cancer. The aim of the present study was to explore the role of Linc00261 in pancreatic cancer (PC). The expression of Linc00261 in patients with PC and PC cell lines was assessed using reverse transcription‑quantitative PCR and the association of Linc00261 expression with survival was analyzed in the online database, GEPIA. The effects of Linc00261 on PC cell metastasis in vitro and in vivo were determined using a wound healing assay, Transwell invasion assays and a nude mouse model of liver metastasis. The relationship between Linc00261, the miR‑552‑5p/forkhead box O3 (FOXO3) axis and the Wnt signaling pathway were determined using bioinformatics analysis, dual luciferase assay and western blotting. Linc00261 expression was significantly decreased in PC tissues and cell lines, and reduced expression was associated with less favorable outcomes in patients with PC. Linc00261 overexpression inhibited migration and invasion of PC cells in vitro, whereas knockdown of Linc00261 increased migration and invasion. Linc00261 overexpression also decreased metastasis of PC cells in vivo. Linc00261 was revealed to directly bind to microRNA (miR)‑552‑5p and to decrease the expression of miR‑552‑5p. In addition, Linc00261 overexpression increased the expression of FOXO3, a target gene of miR‑552‑5p, as well as inhibited the Wnt signaling pathway. Overexpression of miR‑552‑5p in Linc00261‑overexpressing PC cells increased migration and invasion, as well as decreased the expression of FOXO3 and members of the Wnt signaling pathway. Collectively, the present study demonstrated that Linc00261 inhibited metastasis and the Wnt signaling pathway of PC by regulating the miR‑552‑5p/FOXO3 axis. Linc00261 may suppress the development of PC, and serve as a potential biomarker and effective target for the diagnosis and treatment of PC.
PMID: 32020223 DOI: 10.3892/or.2020.7480
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Select item 3202022214.
Oncol Rep. 2020 Jan 29. doi: 10.3892/or.2020.7484. [Epub ahead of print]
Inhibitory mechanism of muscone in liver cancer involves the induction of apoptosis and autophagy.
Qi W1, Li Z2, Yang C1, Jiangshan Dai J1, Zhang Q3, Wang D1, Wu C1, Xia L4, Xu S1.
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Abstract
Traditionally, musk has been used as an analgesic to treat pain associated with cancer. Hepatocellular carcinoma (HCC) is an aggressive tumor; however, patients with liver cancer that received musk were reported to live longer and have a higher quality of life. Thus, the present study aimed to investigate whether muscone, a macrocyclic compound of musk, demonstrated potential as an anti‑liver cancer drug for the non‑surgical treatment of advanced liver cancer. Briefly, liver cancer cells were treated with muscone and the rates of cellular apoptosis and autophagy were investigated using staining techniques and western blotting. The underlying molecular mechanisms of muscone were evaluated using high‑throughput sequencing and the in vitro effects of muscone were subsequently validated in vivo using a nude mouse model. Muscone increased the rates of apoptosis and autophagy in liver cancer cells; the increase in cellular apoptosis was observed to occur through endoplasmic reticulum stress responses, whereas muscone‑induced autophagy was closely associated with the AMP kinase/mTOR complex 1 signaling pathway. These findings were verified in vivo. Notably, sestrin‑2 expression levels were also significantly decreased in liver cancer tissues compared with paracancerous tissues. In conclusion, the present study suggests that muscone demonstrates potential as an anticancer drug, and the findings of the present study provide the basis for the development of effective anticancer drugs derived from natural compounds.
PMID: 32020222 DOI: 10.3892/or.2020.7484
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Select item 3202022115.
Oncol Rep. 2020 Jan 13. doi: 10.3892/or.2020.7461. [Epub ahead of print]
DNA aneuploidy and tissue architecture in oral potentially malignant disorders with epithelial dysplasia assessed by a 10 locus FISH panel.
Zaini ZM1, Neat M2, Stokes A1, Tavassoli M3, Odell EW1.
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Abstract
Subjectivity in oral dysplasia grading has prompted evaluation of molecular‑based tests to predict malignant transformation. Aneuploidy detected by DNA image‑based cytometry (ICM) is currently the best predictor but fails to detect certain high risk lesions. A novel multiplex fluorescence in situ hybridization (FISH) panel was used to explore possible explanations by detecting aneuploidy at the single cell level. FISH was compared to reference standard DNA ICM in 19 oral lesions with epithelial dysplasia and used to characterize the cellular architecture. Copy number variation at 3q28, 7p11.2, 8q24.3, 11q13.3 and 20q13.12 and matched chromosome specific loci were assessed by dual‑color FISH to assess numerical and spatial patterns of copy number increase and gene amplification. FISH revealed wide variation in copy number at different loci. Only low level copy number gain was present and often in only a small proportion of cells, although usually with all or all but one locus (9/12). Four cases showed gene amplification, one at two loci. Some probes revealed an internal presumed clonal structure within lesions not apparent in routine histological examination. Both methods produced similar diagnostic results with concordance in detection of aneuploidy by both methods in 17 out of 19 samples (89%). We have shown that oral dysplastic lesions may contain very few aneuploid cells at a cellular level, high copy number gain is rare and changes appear to arise from large chromosomal fragment duplications. Single stem lines are relatively homogeneous for loci with copy number gain but there is a subclonal structure revealed by gene amplification in some lesions.
PMID: 32020221 DOI: 10.3892/or.2020.7461
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Select item 3202022016.
Oncol Rep. 2020 Jan 22. doi: 10.3892/or.2020.7476. [Epub ahead of print]
Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy.
Ma M1, Lin XH1, Liu HH1, Zhang R1, Chen RX1.
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Abstract
The efficacy of chemotherapy for hepatocellular carcinoma (HCC) remains unsatisfactory, primarily due to inherent self‑defense mechanisms (e.g., mitophagy and autophagy). In the present study, we aimed to explore the pro‑apoptotic effects of targeting mitophagy to potentiate the efficacy of chemotherapy for HCC. HCC cells were subjected to cisplatin, after which cisplatin‑induced mitophagy was quantified by immunofluorescence. Mdivi‑1, a specific dynamin‑related protein 1 (DRP1) inhibitor, was used to study the role of DRP1 in cisplatin‑induced HCC mitophagy. The synergistic effect of cisplatin and the DRP1 inhibitor on HCC was assessed in vitro and in vivo. Accordingly, cisplatin induced mitophagy in surviving HCC cells by activating DRP1. The DRP1 inhibitor (Mdivi‑1) increased the apoptosis of cisplatin‑treated HCC cells by targeting mitophagy. Mechanistically, Mdivi‑1 upregulated Bax and downregulated Bcl‑xL, leading to an increase in mitochondrial membrane permeability and subsequent release of cytochrome c from mitochondria into the cytosol, thereby aggravating cisplatin‑induced apoptosis in HCC cells. Moreover, Mdivi‑1 acted synergistically with cisplatin to suppress HCC xenograft growth in vivo. Our results indicate that targeting cisplatin‑mediated mitophagy increases HCC apoptosis via DRP1 inhibition, providing preclinical proof of concept for combination therapy targeting mitophagy to potentiate the efficacy of chemotherapy.
PMID: 32020220 DOI: 10.3892/or.2020.7476
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Select item 3202021917.
Oncol Rep. 2020 Jan 13. doi: 10.3892/or.2020.7459. [Epub ahead of print]
Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low‑grade glioma.
Zhou L1, Tang H2, Wang F3, Ou S1, Wu T1, Fang Y1, Xu J1, Guo K1.
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Abstract
Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood‑brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB‑D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB‑D exerts anticancer effects against GBM and low‑grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB‑D as a new effective agent in the treatment of GBM and LGG. The ability of CVB‑D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V‑FITC/PI assay. The expression levels of the apoptosis‑associated proteins, namely cleaved caspase‑3 and Bax/Bcl‑2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB‑D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB‑D‑treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis‑associated proteins were increased in CVB‑D‑treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB‑D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB‑D in the treatment of glioma.
PMID: 32020219 DOI: 10.3892/or.2020.7459
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Select item 3202021818.
Oncol Rep. 2020 Jan 29. doi: 10.3892/or.2020.7483. [Epub ahead of print]
[Retracted] Downregulation of NOB1 suppresses the proliferation and tumor growth of non‑small cell lung cancer in vitro and in vivo.
Li Y1, Ma C2, Qian M3, Wen Z1, Jing H1, Qian D1.
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Abstract
Oncol Rep 31: [Related article:] 1271‑1276, 2014; DOI: 10.3892/or.2014.2991. The authors wish to retract their article entitled 'Down-regulation of NOB1 suppresses the proliferation and tumor growth of non‑small cell lung cancer in vitro and in vivo', published in Oncology Reports 31: 1271‑1276, 2014. The authors have identified that the results shown in Fig. 4A did not display a significant level of difference comparing among the groups, which undermines the conclusions stated in the article. In addition, the 'Acknowledgements' section featured an error in terms of the quoted project number. For these reasons, the authors have decided to withdraw this paper from the Journal. All the named authors agree to this retraction. and regret any inconvenience to the readers and to the Editor of Oncology Reports that this retraction will cause.
PMID: 32020218 DOI: 10.3892/or.2020.7483
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Select item 3202021719.
Oncol Rep. 2020 Jan 13. doi: 10.3892/or.2020.7460. [Epub ahead of print]
Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway.
Chen K1, Jiao J1, Xue J1, Chen T1, Hou Y1, Jiang Y1, Qian L1, Wang Y1, Ma Z1, Liang Z1, Sun B1, Ren Q2.
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Abstract
Osteosarcoma is one of the most malignant bone tumors, and its major threats are aggressive invasion and early tumor metastasis, which result in a poor prognosis and high mortality. Accumulating evidence indicates that ginsenoside compound K (CK) has a significant antitumor effect, particularly on the inhibition of proliferation and invasion of numerous human tumors. In the present study, it was revealed that CK inhibited the viability and proliferation of osteosarcoma cells. Moreover, it was demonstrated that CK induced apoptosis and inhibited the migration and invasion of osteosarcoma cells via apoptotic staining, Annexin V/PI staining, and Transwell invasion assays. Furthermore, at the molecular level, the present results confirmed that apoptosis and invasion‑related proteins were regulated by CK, which was possibly related to the blockade of the PI3K/mTOR/p70S6K1 signaling pathway. In summary, the present findings indicated that CK inhibited viability and proliferation, induced apoptosis, and inhibited the migration and invasion of osteosarcoma cells through the PI3K/mTOR/p70S6K1 signaling pathway.
PMID: 32020217 DOI: 10.3892/or.2020.7460
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Select item 3202021620.
Oncol Rep. 2020 Jan 20. doi: 10.3892/or.2020.7473. [Epub ahead of print]
Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines.
Al-Yousef N1, Shinwari Z1, Al-Shahrani B1, Al-Showimi M1, Al-Moghrabi N1.
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Abstract
Restoration of normal DNA promoter methylation and expression states of cancer‑related genes may be an option for the prevention as well as the treatment of several types of cancer. Constitutional promoter methylation of BRCA1 DNA repair associated (BRCA1) gene is linked with a high risk of developing breast and ovarian cancer. Furthermore, hypomethylation of the proto‑oncogene γ synuclein (SNCG) is associated with the metastasis of breast and ovarian cancer and reduced disease‑free survival (DFS). In the present study, we evaluated the potential of curcumin to re‑express hypermethylated BRCA1 and to suppress hypomethylated SNCG in triple‑negative breast cancer (TNBC) cell line HCC‑38, the estrogen receptor‑negative/progesterone receptor‑negative (ER‑/PR‑) cell line UACC‑3199, and the ER+/PR+ cell line T47D. The cells were treated with 5 and 10 µM curcumin for 6 days and with 5‑aza‑2'‑deoxycytidine (5'‑aza‑CdR) for 48 h. Methylation‑specific PCR and bisulfite pyrosequencing assays were used to assess DNA promoter methylation while gene expression levels were analyzed using quantitative real‑time PCR and immunoblotting. We found that curcumin treatment restored BRCA1 gene expression by reducing the DNA promoter methylation level in HCC‑38 and UACC‑3199 cells and that it suppressed the expression of SNCG by inducing DNA promoter methylation in T47D cells. Notably, 5'‑aza‑CdR restored BRCA1 gene expression only in UACC‑3199, and not in HCC‑38 cells. Curcumin‑induced hypomethylation of the BRCA1 promoter appears to be realized through the upregulation of the ten‑eleven translocation 1 (TET1) gene, whereas curcumin‑induced hypermethylation of SNCG may be realized through the upregulation of the DNA methyltransferase 3 (DNMT3) and the downregulation of TET1. Notably, miR‑29b was found to be reversely expressed compared to TET1 in curcumin‑ and 5'‑aza‑CdR‑treated cells, suggesting its involvement in the regulation of TET1. Overall, our results indicate that curcumin has an intrinsic dual function on DNA promoter methylation. We believe that curcumin may be considered a promising therapeutic option for treating TNBC patients in addition to preventing breast and ovarian cancer, particularly in cancer‑free females harboring methylated BRCA1.
PMID: 32020216 DOI: 10.3892/or.2020.7473
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Select item 3202021521.
Oncol Rep. 2020 Jan 22. doi: 10.3892/or.2020.7475. [Epub ahead of print]
Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy.
Chen Y1, Yang Z1, Deng B2, Wu D1, Quan Y3, Min Z1.
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Abstract
Interleukin (IL)‑1β is a member of the IL‑1 family of proteins. IL‑1 receptor antagonist (IL‑1RA) is an agent that binds to the IL‑1 receptor, preventing IL‑1 from transmitting signals to cells. The present study aimed to identify the role of the IL‑1β/1RA axis in epithelial‑mesenchymal transition (EMT), cell invasion, migration, proliferation and clone formation in colorectal cancer (CRC) and to determine its underlying mechanisms of action. Significantly increased expression of both IL‑1β and IL‑1RA was identified in CRC patient data uploaded in The Cancer Genome Atlas database, and in tumor tissues when compared with matched control tissue. High expression of IL‑1β was associated with an increased rate of overall survival and recurrence‑free survival. Further research revealed that the IL‑1β gene was co‑expressed with the IL‑1RA gene in tumors of CRC patients. It was additionally determined that recombinant human (rh)IL‑1β suppressed autophagy as well as EMT in HCT‑116 cells compared with control‑treated cells, whereas rhIL‑1RA exhibited the opposite effect. In addition, autophagy activator rapamycin (RAPA) rescued the inhibition of EMT in rhIL‑1β‑treated HCT‑116 cells. Moreover, rhIL‑1β inhibited cell invasion, migration, proliferation and colony‑formation ability, when compared with a control treatment. Compared with a control treatment rhIL‑1RA promoted cell invasion, migration, proliferation, but had no effect on clone formation ability. Furthermore, both rhIL‑1RA and RAPA rescued inhibition of cell invasion, migration and clone formation ability in rhIL‑1β‑treated HCT‑116 cells. RAPA, but not rhIL‑1RA, rescue inhibited proliferation in rhIL‑1β‑treated HCT‑116 cells compared with controls. In addition, it was confirmed that rhIL‑1β inhibited the growth of subcutaneous xenografts in nude mice, when compared with control treatments. These results indicated that upregulation of the IL‑1β/1RA axis in CRC regulated EMT, cell invasion and migration, proliferation and clone formation via autophagy.
PMID: 32020215 DOI: 10.3892/or.2020.7475
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Select item 3202021422.
Oncol Rep. 2020 Jan 14. doi: 10.3892/or.2020.7464. [Epub ahead of print]
A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer.
Li J1, Li X1, Zhang C2, Zhang C3, Wang H4.
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Abstract
Establishing a prognostic genetic signature closely related to the tumor immune microenvironment (TIME) to predict clinical outcomes is necessary. Using the Gene Expression Omnibus (GEO) database of a non‑small cell lung cancer (NSCLC) cohort and the immune score derived from the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, we applied the least absolute shrinkage and selection operator (LASSO) Cox regression model to screen a 10‑gene signature among the 448 differentially expressed genes and found that the risk prediction models constructed by 10 genes could be more sensitive to prognosis than TNM (Tumor, Lymph node and Metastasis) stage (P=0.006). The CIBERSORT method was applied to quantify the relative levels of different immune cell types. It was found that the ratio of eosinophils, mast cells (MCs) resting and CD4 T cells memory activated in the low‑risk group was higher than that in the high‑risk group, and the difference was statistically significant (P=0.003, P=0.014 and P=0.018, respectively). Inconsistently, the ratio of resting natural killer (NK) cells and activated plasma cells in the low‑risk group was significantly lower than that in the high‑risk group (P=0.05 and P=0.009, respectively). Kaplan‑Meier survival results showed that patients of the high‑risk group had significantly shorter overall survival (OS) than those of the low‑risk group in the training set (P<0.001). Furthermore, Kaplan‑Meier survival showed that patients of the high‑risk group had significantly shorter OS than those of the low‑risk group (P=0.0025 and P=0.0157, respectively) in the validation set [GSE31210 and TCGA (The Cancer Genome Atlas)]. The 10‑gene signature was found to be an independent risk factor for prognosis in univariate and multivariate Cox proportional hazard regression analyses (P<0.001). In addition, it was found that the risk model constructed by the 10‑gene signature was related to the clinical related factors in logistic regression analysis. The genetic signature closely related to the immune microenvironment was found to be able to predict differences in the proportion of immune cells (eosinophils, resting MCs, memory activated CD4 T cells, resting NK cells and plasma cells) in the risk model. Our findings suggest that the genetic signature closely related to TIME could predict the prognosis of NSCLC patients, and provide some reference for immunotherapy.
PMID: 32020214 DOI: 10.3892/or.2020.7464
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Select item 3202021323.
Oncol Rep. 2020 Jan 15. doi: 10.3892/or.2020.7468. [Epub ahead of print]
An albumin‑binding domain and targeting peptide‑based recombinant protein and its enediyne‑integrated analogue exhibit directional delivery and potent inhibitory activity on pancreatic cancer with K‑ras mutation.
Sheng W1, Geng J1, Li L1, Shang Y1, Jiang M1, Zhen Y1.
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Abstract
Efficient enrichment and transmembrane transport of cytotoxic reagents are considered to be effective strategies to increase the efficiency and selectivity of antitumor drugs targeting solid tumors. In the present study, a recombinant protein ABD‑LDP‑Ec consisting of the albumin‑binding domain (ABD), the apoprotein (LDP) of lidamycin (LDM) and an EGFR‑targeting oligopeptide (Ec) was prepared by DNA recombination and bacterial fermentation, and was integrated with the enediyne chromophore (AE) of lidamycin to generate its enediyne‑integrated analogue ABD‑LDP‑Ec‑AE. ABD‑LDP‑Ec exhibited high binding capacity to both albumin and EGFR‑positive pancreatic cancer cells, and was internalized into the cytoplasm through receptor‑mediated endocytosis and albumin‑driven macropinocytosis of K‑ras mutant cells. In animal experiments, ABD‑LDP‑Ec demonstrated notable selective distribution in pancreatic carcinoma xenografts by passive targeting of albumin captured in the blood and was retained in the tumor for 48 h. ABD‑LDP‑Ec and ABD‑LDP‑Ec‑AE exhibited inhibitory activity in cell proliferation and AsPC‑1 xenograft growth, and ABD‑LDP‑Ec‑AE increased the tumor growth inhibition rate by 20% compared with natural LDM. The results indicated that the introduction of ABD‑based multi‑functional drug delivery may be an effective approach to improve the efficacy of antitumor drugs, especially for K‑ras mutant cancers.
PMID: 32020213 DOI: 10.3892/or.2020.7468
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Select item 3202021224.
Oncol Rep. 2020 Jan 21. doi: 10.3892/or.2020.7474. [Epub ahead of print]
TGM3 functions as a tumor suppressor by repressing epithelial‑to‑mesenchymal transition and the PI3K/AKT signaling pathway in colorectal cancer.
Feng Y1, Ji D1, Huang Y1, Ji B2, Zhang Y1, Li J2, Peng W1, Zhang C1, Zhang D1, Sun Y1, Xu Z1.
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Abstract
The dysregulation of transcription factors contributes to the unlimited proliferation of cancer cells. Transglutaminase 3 (TGM3) has been demonstrated to play a crucial role in physiology and pathology. However, the potential role of TGM3 in colorectal cancer (CRC) remains unknown. In the present study, reverse transcription‑quantitative PCR and immunohistochemistry were utilized to analyze the expression of TGM3 in CRC and adjacent normal tissues. LoVo and HCT116 cell lines were then selected to further investigate the function of TGM3 in the proliferation, invasion and metastasis of CRC both in vitro and in vivo. Finally, western blotting was performed to investigate the molecular mechanisms underlying the effects of TGM3 in CRC. The expression level of TGM3 was significantly downregulated in CRC tissues, and was associated with tumor invasion, metastasis and patient prognosis. Following TGM3 inhibition and overexpression in CRC cells, it was revealed that TGM3 suppressed cell proliferation, potentially via the promotion of apoptosis and cell cycle regulation. Furthermore, TGM3 also inhibited invasion and metastasis. Finally, it was observed that TGM3 inhibited epithelial‑to‑mesenchymal transition and activated phosphorylated AKT serine/threonine kinase in CRC cells. The results from the present study revealed that TGM3 is a tumor suppressor in the progression of CRC, and may be used as a novel target for CRC treatment.
PMID: 32020212 DOI: 10.3892/or.2020.7474
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Select item 3202021125.
Oncol Rep. 2020 Jan 17. doi: 10.3892/or.2020.7471. [Epub ahead of print]
Downregulation of GPSM2 is associated with primary resistance to paclitaxel in breast cancer.
Zhang Z1, Li Z2, Deng M3, Liu B4, Xin X5, Zhao Z1, Zhang Y6, Lv Q1.
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Abstract
Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20‑30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.
PMID: 32020211 DOI: 10.3892/or.2020.7471
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Select item 3202021026.
Oncol Rep. 2020 Jan 20. doi: 10.3892/or.2020.7472. [Epub ahead of print]
PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells.
Yang K1, Tang XJ2, Xu FF1, Liu JH1, Tan YQ1, Gao L1, Sun Q1, Ding X1, Liu BH1, Chen QX1.
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Abstract
Glioblastoma (GBM) is the most common type of primary central nervous system tumor in adults, which has high mortality and morbidity rates, and short survival time, namely <15 months after the diagnosis and application of standard therapy, which includes surgery, radiation therapy and chemotherapy; thus, novel therapeutic strategies are imperative. The activation of the PI3K/AKT signaling pathway plays an important role in GBM. In the present study, U87 and U251 GBM cells were treated with the PI3K/mTORC1/2 inhibitor PQR309, and its effect on glioma cells was investigated. Cell Counting Kit‑8 assay, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays revealed dose‑ and time‑dependent cytotoxicity in glioma cells that were treated with PQR309. Flow cytometry and western blotting revealed that PQR309 can significantly induce tumor cell apoptosis and arrest the cell cycle in the G1 phase. Furthermore, the expression levels of AKT, phosphorylated (p)‑AKT, Bcl‑2, Bcl‑xL, Bad, Bax, cyclin D1, cleaved caspase‑3, MMP‑9 and MMP‑2 were altered. In addition, the migration and invasion of glioma cells, as detected by wound healing, migration and Transwell invasion assays, exhibited a marked suppression after treating the cells with PQR309. These results indicated that PQR309 exerts an antitumor effect by inhibiting proliferation, inducing apoptosis, inducing G1 cell cycle arrest, and inhibiting invasion and migration in human glioma cells. The present study provides evidence supportive of further development of PQR309 for adjuvant therapy of GBM.
PMID: 32020210 DOI: 10.3892/or.2020.7472
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Select item 3202020927.
Oncol Rep. 2020 Jan 17. doi: 10.3892/or.2020.7470. [Epub ahead of print]
Clinical significance of the molecular heterogeneity of gastrointestinal stromal tumors and related research: A systematic review.
Ding H1, Yu X1, Yu Y1, Lao X1, Hang C1, Gao K1, Jia Y1, Yan Z2.
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Abstract
Gastrointestinal stromal tumors (GISTs) are the most commonly observed mesenchymal tumors of the digestive tract, and they originate from the interstitial cells of Cajal. GISTs can be divided into KIT/PDGFRA‑mutant GISTs and wild‑type GISTs based on the presence or absence of KIT/PDGFRA mutations. Wild‑type GISTs can be divided into succinate dehydrogenase complex (SDH)‑deficient GISTs and non‑SDH‑deficient GISTs. Downstream signaling pathways activated by these mutations serve a pivotal role in the development of GISTs and are associated with the biological behavior, including risk stratification, clinical prognosis and drug resistance. Accurate medical care requires accurate molecular diagnosis, which in turn prolongs the survival of patients with GISTs and makes GIST a chronic disease. At present, there is a lack of effective treatment for imatinib/sunitinib/regorafenib resistant patients and KIT/PDGFRA‑WT GISTs, which is undoubtedly a major challenge for future research. The present review summarizes the molecular pathogenesis of GISTs and the progress of related research.
PMID: 32020209 DOI: 10.3892/or.2020.7470
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Select item 3202020828.
Oncol Rep. 2020 Jan 14. doi: 10.3892/or.2020.7466. [Epub ahead of print]
[Corrigendum] MicroRNA‑497 inhibits the proliferation, migration and invasion of human bladder transitional cell carcinoma cells by targeting E2F3.
Zhang Y1, Zhang Z1, Li Z1, Gong D1, Zhan B1, Man X1, Kong C1.
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Abstract
Subsequently to the publication of the above article, the authors have realized that Fig. 4E in their paper contained errors. The image selected to represent the experiment showing the UM‑UC‑3 cells of the siE2F3 group (0 h) was chosen incorrectly during the figure compilation process. A corrected version of Fig. 4 is shown opposite. Note that this error affected neither the interpretation of the data nor the reported conclusions of this work, and all the authors agree to this Corrigendum. The authors apologize to the Editor and the readership of the Journal for this unintentional error, and for any inconvenience caused. [the original article was published in Oncology Reports 36: 1293‑1300, 2016; DOI: 10.3892/or.2016.4923].
PMID: 32020208 DOI: 10.3892/or.2020.7466
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Select item 3202020729.
Oncol Rep. 2020 Jan 15. doi: 10.3892/or.2020.7467. [Epub ahead of print]
Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis.
Chen L1, Ren P2, Zhang Y3, Gong B4, Yu D5, Sun X6.
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Abstract
Radioresistance hinders the therapeutic outcomes of radiotherapy in non‑small cell lung cancer (NSCLC). Although long non‑coding RNAs (lncRNAs) have been demonstrated to participate in the regulation of multiple cell behaviors, whether they can modulate the radiosensitivity of NSCLC and the underlying molecular mechanisms have not been well investigated. In the present study, it was revealed that NSCLC NCI‑H460 cells were more sensitive to ionizing radiation (IR) than A549 cells. Using the RNA‑Seq method, four highly differentially expressed lncRNAs were identified, including the growth arrest‑specific transcript 5 (GAS5), syntaxin binding protein 5 antisense RNA 1 (STXBP5‑AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and X‑inactive specific transcript (XIST), which were predicted to play roles in the acquisition of radiosensitivity. Using real‑time quantitative PCR (qPCR), it was demonstrated that lncRNA GAS5 was significantly upregulated in NCI‑H460 cells but not in A549 cells during IR. Mechanistically, it was demonstrated that overexpression of lncRNA GAS5 decreased the level of microRNA‑21 (miR‑21). Overexpression of lncRNA GAS5 or suppression of miR‑21 markedly increased the IR‑induced cell apoptosis of A549 cells. It was also demonstrated that overexpression of lncRNA GAS5 increased PTEN expression and suppressed Akt phosphorylation through the modulation of miR‑21. Notably, it was revealed that IR enhanced the interaction between lncRNA GAS5 and the miR‑21/PTEN/Akt axis. In summary, the present findings revealed that lncRNA GAS5 has a radiosensitization effect on NSCLC, indicating the potential application of lncRNA GAS5 in NSCLC radiotherapy.
PMID: 32020207 DOI: 10.3892/or.2020.7467
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Select item 3202020630.
Oncol Rep. 2020 Jan 17. doi: 10.3892/or.2020.7469. [Epub ahead of print]
MicroRNA‑29c‑3p acts as a tumor suppressor gene and inhibits tumor progression in hepatocellular carcinoma by targeting TRIM31.
Lv T1, Jiang L1, Kong L1, Yang J1.
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Abstract
Aberrant expression of microRNAs (miRNAs) has been widely reported in many malignant tumors, and dysregulated miRNAs play an important role in the malignant progression of tumors. It has been reported that miR‑29c‑3p expression is dysregulated in tumors and promotes the development of tumors, especially in hepatocellular carcinoma (HCC). However, the specific mechanism of miR‑29c‑3p in HCC is not clear. The present study demonstrated that miR‑29c‑3p was expressed at low levels in HCC patients and cell lines and that its decreased expression was closely related to poor prognosis of HCC patients. Overexpression of miR‑29c‑3p could significantly inhibit the proliferation and migration of HCC cells in vitro and suppress the HCC tumor growth in vivo. The luciferase reporter assay demonstrated that miR‑29c‑3p directly bound to tripartite motif containing 31 (TRIM31) and suppressed TRIM31 expression. Finally, upregulation of TRIM31 could partially abolish the tumor suppressing roles of miR‑29c‑3p in HCC. Overall, miR‑29c‑3p, as a tumor suppressor gene, was revealed to inhibit the malignant progression of HCC by reducing the expression of TRIM31 and may be used as a potential therapeutic target for the precise treatment of HCC.
PMID: 32020206 DOI: 10.3892/or.2020.7469
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