Abstract
BackgroundDysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research.MethodsAbnormally 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.ResultsPCAT6 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.ConclusionPCAT6 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.
Highlights
Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA)
The pituitary gland is located in the sellar region that is surrounded by important nerves and blood vessels, which explains the high incidence of skull base bone erosion, tumor necrosis, and cystic stroke in invasive PA (IPA) patients who are seriously affected by the disease in terms of quality of life [4, 5]
LncRNAs MEG3 and HOTAIR were found associated with the development of non-invasion PA (NIPA) into IPA, as evidence by the decrease in MEG3 level and increase in HOTAIR level during the development transformation of normal pituitary into NIPA and eventually into IPA tissues [9]; lncRNA H19 was up-regulated in IPA, and thereby could be used as a biomarker for PA diagnosis [10]; the knockdown of lncRNA AFAP1-AS1 could suppress cell growth and induce apoptosis in PA [11]; lncRNA SNHG1 had a high level in IPA and could activate the Wnt/beta-catenin pathway in IPA [12]
Summary
Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). LncRNAs have been recognized as the emerging role in the development of most cancers and in modulating the proliferation, metastasis, and apoptosis of cancer cells including PA cells [3, 7, 8]. LncRNAs MEG3 and HOTAIR were found associated with the development of non-invasion PA (NIPA) into IPA, as evidence by the decrease in MEG3 level and increase in HOTAIR level during the development transformation of normal pituitary into NIPA and eventually into IPA tissues [9]; lncRNA H19 was up-regulated in IPA, and thereby could be used as a biomarker for PA diagnosis [10]; the knockdown of lncRNA AFAP1-AS1 could suppress cell growth and induce apoptosis in PA [11]; lncRNA SNHG1 had a high level in IPA and could activate the Wnt/beta-catenin pathway in IPA [12]. Evidence has exhibited that lncRNAs could target some miRNAs to adjust miRNA-mediated targets and further play a role in physiological and pathological processes [3, 16], there is still a lack of research on the target miRNA of PCAT6
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
