BackgroundCircular RNAs are key regulators in human cancers, however, there is a lack of studies on circRNAs’ specific functions in ovarian cancer.MethodsOur study used qRT-PCR to detect the differentially expressed circRNAs between normal ovaries and ovarian cancer tissues. Cell function experiments were performed to verify the role of overexpression and silence of circWHSC1, including MTT assay, cell apoptosis assay, wound healing and Matrigel-coated Transwell assay. In vivo tumorigenesis model was constructed by subcutaneous injection in nude mice. Bioinformatics analysis predicted the possible binding sites of circWHSC1 with miRNAs, and confirmed with dual-luciferase reporter assay and RNA pull-down assay. The exosomes were extracted with ultracentrifugation. HE staining was also used to detect morphology of nude mice peritoneum.ResultsWe found that circWHSC1 was up-regulated in ovarian cancer tissues, and circWHSC1 expression was higher in moderate & poor differentiation ovarian cancer tissues than in well differentiation ovarian cancer tissues. Overexpression of circWHSC1 increased cell proliferation, migration and invasion, and inhibited cell apoptosis. Silence of circWHSC1 exerted the opposite effects. Additionally, circWHSC1 could sponge miR-145 and miR-1182 and up-regulate the expression of downstream targets MUC1 and hTERT. Exosomal circWHSC1 can be transferred to peritoneal mesothelial cells and promotes peritoneal dissemination.ConclusionsOur study demonstrates the highly expressed circWHSC1 in ovarian cancer promotes tumorigenesis by sponging miR-145 and miR-1182, and its exosome forms induce tumor metastasis through acting on peritoneal mesothelium.
Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. The PUM1 gene has been confirmed to be closely related to tumorigenesis and progression of ovarian cancer. In the present study, we explored the function and underlying molecular mechanism of circPUM1 in ovarian cancer. qRT-PCR analysis showed upregulation of circPUM1 in ovarian cancer tissues compared with normal ovaries. Gain- and loss-of-function experiments indicated that circPUM1 increased cell proliferation, migration, and invasion and inhibited cell apoptosis. Intraperitoneal injection of circPUM1-knockout tumor cells in nude mice resulted in a decrease in the metastatic ability of the tumor. Bioinformatics analysis and dual-luciferase reporter assays revealed that circPUM1 upregulated the expression of nuclear factor kappa B (NF-κB) and MMP2 by sponging miR-615-5p and miR-6753-5p. Further studies showed that exosomal circPUM1 acted on peritoneal mesothelial cells and increased tumor metastasis. In conclusion, our study indicates that circPUM1 not only promotes ovarian cancer proliferation, migration and invasion, but also acts on the peritoneum and contributes to metastasis of cancer in the form of cancer-derived exosomes.
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Endometrial carcinoma is one of the most frequently diagnosed cancers in females. Long non-coding RNAs (lncRNAs) have been associated with cancer; its role in endometrial carcinoma is an emerging area of research. In this article, lncRNA TDRG1 expression in human endometrial carcinoma tissues and normal endometrial tissues was quantified by qRT-PCR. LncRNA TDRG1 was overexpressed or knocked-down in neither HEC-1B nor Ishikawa endometrial carcinoma cells, respectively, to assess cellular phenotype and expression of related molecules. Our results showed that lncRNA TDRG1 was significantly overexpressed in endometrial carcinoma tissues. Overexpression of lncRNA TDRG1 promoted endometrial carcinoma cell viability, invasion and migratory ability, inhibited apoptosis, and upregulated VEGF-A, PI3K, Bcl-2, MMP2 and survivin; knockdown of lncRNA TDRG1 had the opposite effects. LncRNA TDRG1 overexpression increased tumorigenicity in vivo and was associated with the upregulation of VEGF-A. RNA binding protein immunoprecipitation (RIP) assays confirmed that lncRNA TDRG1 directly binds to VEGF-A protein. Furthermore, knockdown of VEGFA in lncRNA TDRG1-overexpressing endometrial carcinoma cells reversed the effects of lncRNA TDRG1 on cell proliferation, invasion, migration and apoptosis. In conclusion, lncRNA TDRG1 may promote endometrial carcinoma cell proliferation and invasion by positively targeting VEGF-A and modulating relative genes.
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