MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A

• Main Authors: Chang M, Yan P, Zhang B, Zhang G, Wang J, Ge H, Han N, Du C, Shi W, Tian Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-11-01
• Series: OncoTargets and Therapy
• Subjects: mir-769-5p; glioma; kmt2a; tumor growth; apoptosis
• Online Access: https://www.dovepress.com/microrna-769-5p-promotes-the-growth-of-glioma-cells-by-targeting-lysin-peer-reviewed-article-OTT
• ISSN: 1178-6930

Mingze Chang,1,2 Peng Yan,3 Bei Zhang,4 Gejuan Zhang,1 Juanhong Wang,5,6 Hanming Ge,1 Nannan Han,1 Chengxue Du,1 Wenzhen Shi,1 Ye Tian2 1Department of Neurology, Xi’an No. 3 Hospital, Xi’an 710021, People’s Republic of China; 2Department of Neurology, The Affiliated Hospital of Northwest University, Xi’an 710021, People’s Republic of China; 3The College of Life Sciences, Northwest University, Xi’an 710069, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, People’s Republic of China; 5Department of Pathology, Xi’an No.3 Hospital, Xi’an 710021, People’s Republic of China; 6Departments of Pathology, Xi’an Central Hospital, Xi’an 71000, People’s Republic of ChinaCorrespondence: Ye TianDepartment of Neurology, the Affiliated Hospital of Northwest University, 10 East Section of Fengcheng 3rd Road, Xi’an 710021, People’s Republic of ChinaTel [phone]Email [e-mail]: Accumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated.Methods: The levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma.Results: We found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells.Conclusion: In summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.Keywords: miR-769-5p, glioma, KMT2A, tumor growth, apoptosis