microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1

被引：13

作者：

Liu, Gang ^{[1
]}

Chen, Feng-Li ^{[2
]}

Ji, Feng ^{[1
]}

Fei, Hao-Dong ^{[1
]}

Xie, Yue ^{[1
]}

Wang, Shou-Guo ^{[1
]}

机构：

[1] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Orthoped, Huaian, Peoples R China

[2] Nanjing Med Univ, Huaian Peoples Hosp 1, Clin Lab, Huaian, Peoples R China

来源：

ONCOTARGET | 2018年 / 9卷 / 02期

关键词：

dexamethasone; osteoblasts; microRNA-19a; Tuberous sclerosis complex 1 (TSC1); mTOR complex 1 (mTORC1); INHIBITOR RAD001 EVEROLIMUS; TUBEROUS SCLEROSIS COMPLEX; OXIDATIVE STRESS; CELL-GROWTH; CULTURED OSTEOBLASTS; INDUCED-APOPTOSIS; NONCODING RNA; MTOR; ACTIVATION; CANCER;

D O I：

10.18632/oncotarget.23326

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2017 / 2027

页数：11

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