Ryota Fujii1, Eiji Osaka2, Kentaro Sato1, Yasuaki Tokuhashi1. 1. Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan. 2. Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan osaka.eiji@nihon-u.ac.jp.
Abstract
BACKGROUND/AIM: miRNA-1(miR-1) is down-regulated in various cancer cells including osteosarcoma cells. This study was conducted to analyze the function of miR-1 in osteosarcoma cells. MATERIALS AND METHODS: miR-1 expression in osteosarcoma cells was evaluated by qRT-PCR. Cell proliferation was evaluated after transfecting miR-1 by WST8 assay and FACS analysis, both in vitro and in vivo. RESULTS: Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G0-G1 phase by increasing p21 levels via a p53-independent pathway. Overexpression of miR-1 down-regulated PAX3, a potential p21-regulating gene. Moreover, knockdown of PAX3 suppressed cell proliferation by increasing p21 levels, and induced arrest at the G0/G1 phase. Administration of miR-1 showed an in vivo antitumor effect. CONCLUSION: Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G0/G1 phase by increasing p21 levels via a p53-independent pathway through PAX3 suppression. These results indicate that miR-1 could be a therapeutic target for osteosarcoma. Copyright
BACKGROUND/AIM: miRNA-1(miR-1) is down-regulated in various cancer cells including osteosarcoma cells. This study was conducted to analyze the function of miR-1 in osteosarcoma cells. MATERIALS AND METHODS:miR-1 expression in osteosarcoma cells was evaluated by qRT-PCR. Cell proliferation was evaluated after transfecting miR-1 by WST8 assay and FACS analysis, both in vitro and in vivo. RESULTS: Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G0-G1 phase by increasing p21 levels via a p53-independent pathway. Overexpression of miR-1 down-regulated PAX3, a potential p21-regulating gene. Moreover, knockdown of PAX3 suppressed cell proliferation by increasing p21 levels, and induced arrest at the G0/G1 phase. Administration of miR-1 showed an in vivo antitumor effect. CONCLUSION: Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G0/G1 phase by increasing p21 levels via a p53-independent pathway through PAX3 suppression. These results indicate that miR-1 could be a therapeutic target for osteosarcoma. Copyright