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

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...

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Published in:Journal of Huazhong University of Science and Technology. Medical sciences Vol. 34; no. 6; pp. 889 - 895
Main Author: 林松 邵楠楠 范磊 马秀才 浦飞飞 邵增务
Format: Journal Article
Language:English
Published: Heidelberg Huazhong University of Science and Technology 01-12-2014
Department of Orthopaedics, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China%Department of Radiology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China
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Summary: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.
Bibliography: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.
Song LIN , Nan-nan SHAO , Lei FAN , Xiu-cai MA , Fei-fei PU , Zeng-wu SHAO (1 Department of Orthopaedics, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China ;2 Department of Radiology, Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China)
42-1679/R
miR- 101; mTOR; osteosarcoma; proliferation; apoptosis
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1672-0733
1993-1352
DOI:10.1007/s11596-014-1369-y