Frontiers in Oncology (Sep 2020)
A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer
Abstract
BackgroundAccumulating studies have revealed that long non-coding RNA (lncRNA) and microRNA (miRNA) contribute to ovarian cancer (OC). DSCR8 has been found to mediate hepatocellular carcinoma development, while its role in OC remains to be explored.MethodsIn this study, lncRNA DSCR8 and miR-98-5p expressions in OC tissues and adjacent non-cancer tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Besides, gain-of-function or loss-of-function assays of DSCR8 and miR-98-5p were conducted on OC cell lines SKOV-3 and A2780. Cell proliferation was detected with Cell Counting Kit (CCK)8 and colony formation assay, and western blot was used to test the apoptotic levels of OC cells. Transwell assay was conducted to examine cell invasion, and the epithelial–mesenchymal transition (EMT) of OC cells was tested by western blot. Moreover, luciferase activity assay and RNA immunoprecipitation (RIP) assay were conducted to verify the relationships between DSCR8 and miR-98-5p, miR-98-5p, and signal transducer and activator of transcription 3 (STAT3).ResultsDSCR8 was remarkedly increased in OC tissues and associated with poorer survival of OC patients. Overexpressing DSCR8 promoted cell proliferation, invasion, and EMT but inhibited apoptosis. On the other hand, miR-98-5p was downregulated in OC tissues and relieved the progression of OC. Moreover, overexpressed DSCR8 increased the levels of STAT3 and hypoxia inducible factor 1 alpha (HIF-1α) and dampened the functions of miR-98-5p on OC. Pharmaceutical intervention of STAT3 and HIF-1α significantly altered the expressions of DSCR8 and miR-98-5p.ConclusionThe present results suggested a positive feedback loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-α axis in the progression of OC.
Keywords
