title: 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.
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West District of Anhui Provincial Hospital, Hefei 230031, Anhui, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West District of Anhui Provincial Hospital, Hefei 230031, Anhui, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Clinical Geriatrics, Anhui Provincial Hospital, Hefei 230031, Anhui, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Anhui Cancer Hospital, West District of Anhui Provincial Hospital, Hefei 230031, Anhui, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Xinxiang Medical University, Xinxiang 453000, Henan, China.
authors.forename: Yinpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West District of Anhui Provincial Hospital, Hefei 230031, Anhui, China.|Department of Orthopedic Surgery, Anhui Cancer Hospital, West District of Anhui Provincial Hospital, Hefei 230031, Anhui, China.
authors.forename: Shanbao
authors.initials: S
authors.lastname: Cai
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019009:Proto-Oncogene Proteins c-kit
keywords: CD117; miR-34a-5p; multi-drug resistance; osteosarcoma