Oncotarget

Research Papers:

miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway

Chun Zhou, Chang-Qing Jiang, Zhen Zong, Jia-Chen Lin and Li-Feng Lao _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:74276-74286. https://doi.org/10.18632/oncotarget.19395

Metrics: PDF 1090 views  |   HTML 1751 views  |   ?  


Abstract

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

Correspondence to:

Li-Feng Lao, email: laolifeng03@163.com

Keywords: miR-146a-5p, growth, ZNRF3, osteosarcoma, recurrence

Received: April 09, 2017    Accepted: June 19, 2017    Published: July 19, 2017

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 19395