Fujii Ryota, Osaka Eiji, Sato Kentaro, Tokuhashi Yasuaki
Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan.
Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan
Cancer Genomics Proteomics. 2019 Jan-Feb;16(1):71-79. doi: 10.21873/cgp.20113.
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.
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.
Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G-G 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 G/G phase. Administration of miR-1 showed an in vivo antitumor effect.
Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G/G 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.
背景/目的：微小RNA-1（miR-1）在包括骨肉瘤细胞在内的多种癌细胞中表达下调。本研究旨在分析miR-1在骨肉瘤细胞中的功能。
采用qRT-PCR评估骨肉瘤细胞中miR-1的表达。通过WST8检测和流式细胞术分析，在体外和体内转染miR-1后评估细胞增殖情况。
miR-1的过表达通过不依赖p53的途径增加p21水平，从而抑制细胞增殖并诱导细胞周期停滞在G₀/G₁期。miR-1的过表达下调了PAX3，这是一个潜在的p21调节基因。此外，敲低PAX3通过增加p21水平抑制细胞增殖，并诱导细胞停滞在G₀/G₁期。给予miR-1显示出体内抗肿瘤作用。
miR-1的过表达通过抑制PAX3，以不依赖p53的途径增加p21水平，从而抑制细胞增殖并诱导细胞停滞在G₀/G₁期。这些结果表明，miR-1可能是骨肉瘤的治疗靶点。
