Oncotarget

Research Papers:

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1

Gang Liu, Feng-Li Chen, Feng Ji _, Hao-Dong Fei, Yue Xie and Shou-Guo Wang

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Oncotarget. 2018; 9:2017-2027. https://doi.org/10.18632/oncotarget.23326

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Abstract

Gang Liu1,*, Feng-Li Chen2,*, Feng Ji1, Hao-Dong Fei1,*, Yue Xie1 and Shou-Guo Wang1

1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

2Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

*Co-first authors

Correspondence to:

Feng Ji, email: huaiaifengjidr@163.com

Shou-Guo Wang, email: shouguoha126@126.com

Keywords: dexamethasone; osteoblasts; microRNA-19a; tuberous sclerosis complex 1 (TSC1); mTOR complex 1 (mTORC1)

Received: September 11, 2017     Accepted: December 08, 2017     Published: December 15, 2017

ABSTRACT

Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a (“miR-19a”, -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling.


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