微小RNA-19a通过靶向结节性硬化症复合物1（TSC1）保护成骨细胞免受地塞米松的影响。

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1.

作者信息

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

机构信息

Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

Clinical Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.

出版信息

Oncotarget. 2017 Dec 15;9(2):2017-2027. doi: 10.18632/oncotarget.23326. eCollection 2018 Jan 5.

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 . 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.

雷帕霉素靶蛋白复合物1（mTORC1）的激活可保护人成骨细胞免受地塞米松的影响。结节性硬化复合物1（TSC1）是mTORC1的上游抑制蛋白。我们在此证明，微小RNA-19a（“miR-19a”，-3p）靶向……的3'非翻译区。miR-19a的表达下调了OB-6成骨细胞和原代人成骨细胞中的TSC1。miR-19a激活了mTORC1并保护人成骨细胞免受地塞米松的影响。通过RAD001或Raptor短发夹RNA抑制mTORC1，几乎完全消除了miR-19a诱导的成骨细胞对地塞米松的细胞保护作用。通过靶向短发夹RNA敲低TSC1同样诱导了mTORC1的激活并保护了成骨细胞。此外，miR-19a激活了mTORC1依赖性的核因子E2相关因子2（Nrf2）信号通路，并抑制了地塞米松诱导的成骨细胞中活性氧的产生。总之，miR-19a可能通过靶向TSC1-mTORC1信号通路保护人成骨细胞免受地塞米松的影响。