Open AccessmiR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway
Author(s) -
Chun Zhou,
Chuanhai Jiang,
Zhen Zong,
Jiachen Lin,
Li Lao
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.19395
Subject(s) - gene knockdown , osteosarcoma , oncogene , cell growth , microrna , cancer research , medicine , in vivo , biology , oncology , cell culture , gene , cell cycle , cancer , genetics
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.