Proliferation and invasion of ovarian cancer cells are suppressed by knockdown of TRIM11.
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ABSTRACT:
SUBMITTER: Chen Y
PROVIDER: S-EPMC5530193 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Ovarian cancer typically is diagnosed late because insensitivity and lack of specificity of current biomarkers prior to its clinical detection. Ribosomal protein S6 (RPS6) is a ribosomal protein involved in the ribosomal 40S subunit, but its biological role in epithelial ovarian cancer (EOC) is still unknown. RESULTS:RPS6 was elevated in EOC compared to normal ovarian tissues and adenomas. Higher expression of RPS6 predicted worse prognosis in EOC. The level of RPS6 was correlated with clinical stage, histological type and pathological grade. Knockdown of RPS6 reduced the proliferation of ovarian cancer cell lines SKOV-3 and HO8910, and inhibit the migration and invasion ability. It revealed that cells arrested at G0G1 phase after knockdown of RPS6, and the expressions of CyclinD1, Cyclin E, CDK2, CDK4, CDK6 and pRb were also reduced. CONCLUSIONS:RPS6 is involved in EOC and knockdown of RPS6 could inhibit the proliferation, invasion and migration ability of EOC in vitro by inducing G0/G1 phase arrest. RPS6 is expected to be a novel biomarker and molecular target to the EOC.
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Project description:CREBBP, in short CBP, has been reported to be involved in tumorigenesis in various cancers, but its role in ovarian cancer remains largely unexplored. In our study, survival analysis of CBP in patients with ovarian cancer was conducted using the Kaplan-Meier Plotter database, then we utilized specific shRNA targeting CREBBP to block the expression of CBP, and detected its effect on cell proliferation and chemo-sensitivity in ovarian cancer cells. The results showed that high expression of CBP was correlated with poor prognosis in ovarian cancer patients. CREBBP knockdown in ovarian cancer cells significantly inhibited tumor proliferation both in vitro and in vivo. Moreover, CREBBP knockdown promoted chemo-sensitivity in ovarian cancer cells. Mechanism research further demonstrated that CREBBP knockdown attenuated unfolded protein response (UPR), which was mediated by PERK/ATF4/STC2 signaling pathway. Our research linked CBP and UPR in ovarian cancer and may provide new strategies for the clinical treatment of ovarian cancer.
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Project description:AimN6-methyladenosine (m6A) RNA methylation exerts a regulatory effect on endometrioid ovarian cancer (EOC), but the specific m6A regulator genes in EOC remain to be explored. This study investigated that sulforaphene (Sul) is implicated in EOC development by regulating methyltransferase-like 3 (METTL3).MethodsThe dysregulated m6A RNA methylation genes in EOC were determined by methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing. The roles of METTL3 and/or Sul on viability, proliferative ability, cell cycle, and apoptosis of EOC cells were determined by MTT, colony formation, flow cytometry, and TUNEL staining assay, respectively. The expression of METTL3 and apoptosis-related proteins in EOC cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays.ResultsFive m6A RNA methylation regulators (METTL3, ELF3, IGF2BP2, FTO, and METTL14) were differentially expressed in EOC, among which METTL3 had the highest expression level. Silencing METTL3 reduced the clonal expansion and viability of EOC cells, and caused the cells to arrest in the G0/G1 phase. This also promoted apoptosis in the EOC cells and activated the FAS/FADD and mitochondrial apoptosis pathways. In contrast, overexpressing METTL3 had the opposite effect. Sul, in a dose-dependent manner, reduced the viability of EOC cells but promoted their apoptosis. Sul also increased the levels of IGF2BP2 and FAS, while decreasing the levels of KRT8 and METTL3. Furthermore, Sul was able to reverse the effects of METTL3 overexpression on EOC cells.ConclusionsSul could suppress cell proliferation and promote apoptosis of EOC cells by inhibiting the METTL3 to activate the FAS/FADD and apoptosis-associated pathways.
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Project description:ObjectiveTo investigate the role of selenocysteine-tRNA specific eukaryotic elongation factor (EEFSEC) in regulating the proliferation, migration, and invasion of human prostate cancer 22Rv1 cells.MethodsWe detected EEFSEC mRNA expression levels in human normal prostate cell line RWPE1 and human prostate cancer cell lines 22Rv1, LNCaP, Vcap and PC-3 using qRT-PCR and EEFSEC protein expression in surgical specimens of prostate cancer and adjacent tissues using Western blotting. 22Rv1 cells were infected with a lentiviral vector carrying EEFSEC shRNA or a control lentivirus and the interference efficiency was determined using Western blotting. XTT assay was used to assess the changes in the viability of the infected cells, and Transwell chamber assay was used to examine the changes in cell migration and invasion. The effect of EEFSEC knockdown on cell cycle progression was determined with flow cytometry and by detecting the expressions of cell cycle proteins using qRT-PCR.ResultsEEFSEC was significantly upregulated in prostate cancer cells (P < 0.05), and a high expression of EEFSEC was associated with a poor prognosis of the patients with prostate cancer. In 22Rv1 cells, EEFSEC knockdown significantly suppressed the proliferation (P < 0.001), migration (P < 0.001) and invasion (P < 0.001) of the cells, resulted in cell cycle arrest in G0/G1 phase, obviously inhibited the expression of C-myc and CCNB1, and significantly increased the expression of p15.ConclusionEEFSEC knockdown can inhibit the proliferation, migration, and invasion of prostate cancer cells in vitro possibly by down-regulating the expression of C-myc.
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