title: miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression.
abstract: The ability of osteosarcoma cells to form lung metastases has been inversely correlated to cell surface Fas expression. Downregulation of Fas allows osteosarcoma cells to circumvent FasL-mediated apoptosis upon entrance into the FasL(+) lung microenvironment. However, the mechanism of Fas regulation remains unclear. Here, we show that miRNA plays a role in the downregulation of Fas expression in osteosarcoma. Expression levels of several members of the miR-17-92 cluster including miR-20a and miR-19a were found to be higher in metastatic low-Fas-expressing LM7 cells than in the parental nonmetastatic high-Fas-expressing SAOS-2 cells. We also found an inverse correlation between Fas and miR-20a expression in all 8 cell lines derived from patient samples. Overexpression of miR-20a consistently resulted in the downregulation of Fas expression in SAOS-2 cells and thus in decreased sensitivity to FasL. Conversely, inhibiting miR-20a in LM7 cells increased Fas expression and their sensitivity to FasL. Mice injected with LM7 stably transfected with anti-miR-20a had fewer metastases than those with control plasmids. Taken together, our findings suggest that miR-20a, encoded by miR-17-92, downregulates Fas expression in osteosarcoma, thus contributing to the metastatic potential of osteosarcoma cells by altering the phenotype and allowing survival in the FasL(+) lung microenvironment.
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Gangxiong
authors.initials: G
authors.lastname: Huang
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Nishimoto
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhou
authors.forename: Dennis
authors.initials: D
authors.lastname: Hughes
authors.forename: Eugenie S
authors.initials: ES
authors.lastname: Kleinerman
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D062085:RNA, Long Noncoding; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; C568997:MIR17HG, human; C549214:MIRN19A microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C532375:Mirn20 microRNA, mouse; D062085:RNA, Long Noncoding; D019014:fas Receptor