MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo-resistance via ZNRF2

// Qiang Xiao 1 , Yu Yang 1 , Qing An 1 and Yong Qi 1 1 Department of Hand Surgery, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China Correspondence to: Qiang Xiao, email: qiang_xiao14@163.com , xx6990@sina.com.cn Keywords: osteosarcoma (OS), ZNRF2, miR-100, cancer growth, chemo-resistance Received: January 23, 2017     Accepted: February 15, 2017     Published: March 13, 2017 ABSTRACT Osteosarcoma (OS) is a prevalent cancer worldwide. MicroRNAs (miRNAs) play critical roles in the growth, invasion and carcinogenesis of OS, whereas the underlying mechanisms remain ill-defined. Here, we addressed these questions. We detected significantly higher levels of ZNRF2, a ubiquitin ligase of the RING superfamily, and significantly lower levels of miR-100 in the OS specimens, compared to the paired normal bone tissues. The levels of ZNRF2 and miR-100 inversely correlated in the OS specimens. In addition, low miR-100 levels are associated with poor prognosis of the OS patients. Either ZNRF2 overexpression or miR-100 depletion increased in vitro OS cell growth and improved cell survival at the presence of Doxorubicin. Mechanistically, with the help of bioinformatics analysis and luciferase-reporter assay, we found that miR-100 might bind to the 3’-UTR of ZNRF2 mRNA to prevent its protein translation. Thus, our data suggest that re-expression of miR-100 may inhibit OS cell growth and decrease OS cell chemo-resistance.