miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway
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Chun Zhou1, Chang-Qing Jiang1, Zhen Zong1, Jia-Chen Lin1 and Li-Feng Lao1
1Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Li-Feng Lao, email: [email protected]
Keywords: miR-146a-5p, growth, ZNRF3, osteosarcoma, recurrence
Received: April 09, 2017 Accepted: June 19, 2017 Published: July 19, 2017
MicroRNA-146a-5p (miR-146a) functions as a tumor suppressor or oncogene involved in multiple biological processes. But, the underlying molecular mechanisms by which miR-146a contributes to osteosarcoma (OS) remain unclear. The correlation of miR-146a expression with clinicopathologic characteristics and prognosis of OS patients was analyzed by Kaplan-Meier and Cox regression analysis. Cell growth in vitro and in vivo was assessed by MTT, cell colony formation and animal models. The target of miR-146a was identified by bioinformatics software and gene luciferase reporter. As a result, miR-146a expression was substantially elevated in OS tissues and was positively associated with the tumor size (P=0.001) and recurrence (P=0.027) of OS patients. Moreover, knockdown of miR-146a suppressed cell proliferation and colony formation in vitro and in vivo. In addition, zinc and ring finger 3 (ZNRF3) was identified as a direct target of miR-146a in OS cells, and was negatively correlated with miR-146a expression in OS tissues. Overexpression of ZNRF3 inhibited cell growth and rescued the tumor-promoting role of miR-146a via inhibition of GSK-3β/β-catenin signaling pathway. Taken together, miR-146a may function as an oncogene in OS cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway, and represent a promising biomarker for OS patients.
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