LncRNA-MEG3 inhibits cell proliferation of endometrial carcinoma by repressing Notch signaling

• Published in: Biomedicine & pharmacotherapy Vol. 82; pp. 589 - 594
• Main Authors: Guo, Qingyun, Qian, Zhida, Yan, Dingding, Li, Li, Huang, Lili
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-08-2016
• Subjects: Animals; Cell Line, Tumor; Cell Proliferation; Down-Regulation - genetics; Endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Internal Medicine; Male; Medical Education; MEG3; Mice, Nude; Notch signaling; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Transcription Factor HES-1 - genetics; Transcription Factor HES-1 - metabolism; Up-Regulation - genetics; Xenograft Model Antitumor Assays; Cell proliferation; MEG3; Notch signaling; Endometrial carcinoma
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.02.049

Abstract Background The long non-coding RNA MEG3 has shown functional role as a tumor suppressor in many cancer types, excluding endometrial carcinoma (EC). Thus, this study tried to reveal the MEG3 dysregulation in EC samples and potential functional mechanism due to its regulation on Notch signaling pathway. Methods The expression profiles of MEG3 and two Notch signaling molecules, Notch1 and Hes1, were detected in both EC tissues and cell lines through real time PCR and western blot analysis. Lentiviral vector carrying whole MEG3 transcript or shRNA targeting MEG3 (shMEG3) was transfected for MEG3 dysfunction studies, and cell proliferation was analyzed through MTT and colony-formation assays. Xenograft models were also established by subcutaneous implantation and tumor growth was compared under MEG3 dysregulation. Results Significant downregulation of MEG3 was observed in EC samples compared to control, while the protein levels of Notch1 and Hes1 were both upregulated. Cell proliferation was obviously inhibited by MEG3 overexpression, while opposite improved result was obtained in MEG3 knockout cells. Interestingly, MEG3-induced changes could be reversed by Notch1 regulators. Moreover, MEG3 overexpressing tumors showed strongly repressed growth in vivo , along with Notch signaling inhibition. Conclusion Downregulated MEG3 exhibited an anti-proliferative role in EC by repressing Notch signaling pathway.