LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis

Abstract

Abstract Background Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. Methods Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were determined by bioinformatics, dual-luciferase reporter assay, or RIP. The correlation among PCAT6, miR-139-3p, and BRD4 was further analyzed. The viability, apoptosis, cell cycle distribution of PA cells, as well as their ability to invade, migrate, and proliferate, were tested after transfection through CCK-8, flow cytometry, transwell, wound healing, and colony formation assays. After construction of transplanted-tumor model in nude mice, cell apoptosis in the tumor was detected by TUNEL. The expressions of PCAT6, BRD4, miR-139-3p, and apoptosis-related factors in PA tissues, cells, or tumor tissues were detected by RT-qPCR, Western blot, or IHC. Results PCAT6 and BRD4 were high-expressed but miR-139-3p was low-expressed in PA. Both the 3′-untranslated regions of PCAT6 and BRD4 mRNAs were demonstrated to contain a potential binding site for miR-139-3p. PCAT6 was positively correlated to BRD4, and miR-139-3p was negatively correlated to PCAT6 and BRD4. MiR-139-3p mimic, shPCAT6 and siBRD4 inhibited the viability, migration, invasion, and proliferation of PA cells while inducing apoptosis. MiR-139-3p mimic and shPCAT6 inhibited the cell cycle progression of PA cells, decreased the weight and volume of the xenotransplanted tumor, and reduced the levels of Bcl-2 and BRD4 while enhancing the levels of Bax, miR-139-3p, and Cleaved caspase-3. MiR-139-3p inhibitor caused the opposite effect of miR-139-3p mimic and further reversed the effect of shPCAT6 on on PA cells. Conclusion PCAT6 regulated the progression of PA via modulating the miR-139-3p/BRD4 axis, which might provide a novel biomarker for the prevention, diagnosis, and treatment of PA.