MiR-34a-5p promotes the multi-drug resistance of osteosarcoma by targeting the CD117 gene.

Abstract

An association has been reported between miR-34a-5p and several types of cancer. Specifically, in this study, using systematic observations of multi-drug sensitive (G-292 and MG63.2) and resistant (SJSA-1 and MNNG/HOS) osteosarcoma (OS) cell lines, we showed that miR-34a-5p promotes the multi-drug resistance of OS through the receptor tyrosine kinase CD117, a direct target of miR-34a-5p. Consistently, the siRNA-mediated repression of CD117 in G-292 and MG63.2 cells led to a similar phenotype that exhibited all of the miR-34a-5p mimic-triggered changes. In addition, the activity of the MEF2 signaling pathway was drastically altered by the forced changes in the miR-34a-5p or CD117 level in OS cells. Furthermore, si-CD117 suppressed the enhanced colony and sphere formation, which is in agreement with the characteristics of a cancer stem marker. Taken together, our data established CD117 as a direct target of miR-34-5p and demonstrated that this regulation interferes with several CD117-mediated effects on OS cells. In addition to providing new mechanistic insights, our results will provide an approach for diagnosing and chemotherapeutically treating OS.