Effect of MicroRNA-101 on Proliferation and Apoptosis of Human Osteosarcoma Cells by Targeting mTOR

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2014-12, Vol.34 (6), p.889-895
• Main Author: 林松 邵楠楠 范磊 马秀才 浦飞飞 邵增务
• Format: Article
• Language: English
• Subjects: Apoptosis; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Humans; Medicine; Medicine & Public Health; MicroRNAs - genetics; MicroRNAs - metabolism; mTOR; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; 信号; 生物信息; 细胞凋亡; 细胞增殖; 细胞系; 肿瘤生长; 骨肉瘤
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-014-1369-y

Studies have proved that microRNA-101 （miR-101） functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in os- teosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptusis have not been fully elucidated. In this study, we found that the expression ofmiR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthe- sized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR- 101. Overexpression of miR- 101 significantly decreased the ex- pression of roTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting ceils apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells, roTOR plays an important role in mediating miR-101 dependent bio- logical functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy bydown-regulating mTOR expression.