OncoTargets and Therapy (Nov 2019)
MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A
Abstract
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 +86-029-87268355Email [email protected]: 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
