Oncotarget

Research Papers:

MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone

Sai Zhao, Li Mao, Shou-Guo Wang _, Feng-Li Chen, Feng Ji and Hao-Dong Fei

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Oncotarget. 2017; 8:104867-104876. https://doi.org/10.18632/oncotarget.20452

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Abstract

Sai Zhao1,*, Li Mao2,*, Shou-Guo Wang3, Feng-Li Chen4, Feng Ji3 and Hao-Dong Fei3

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

2Department of Endocrinology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

3Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

4Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

*Co-first authors

Correspondence to:

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

Feng Ji, email: huaiaifengjidr@163.com

Keywords: dexamethasone; osteoblasts; miR-200a; keap1; Nrf2

Received: May 23, 2017    Accepted: July 13, 2017    Published: August 24, 2017

ABSTRACT

Treatment with dexamethasone in human osteoblasts leads to oxidative stress and cell injures. NF-E2-related factor 2 (Nrf2) is a key anti-oxidant signaling. We want to induce Nrf2 activation via microRNA-mediated silencing its suppressor Keap1. Our results show that microRNA-200a (“miR-200a”) expression depleted Keap1, causing Nrf2 protein stabilization in OB-6 osteoblastic cells. Reversely, the miR-200a anti-sense led to Keap1 upregulation and Nrf2 degradation. miR-200a expression activated Nrf2 signaling, which inhibited dexamethasone-induced reactive oxygen species production and OB-6 cell death/apoptosis. Keap1 shRNA also activated Nrf2 and protected OB-6 cells from dexamethasone. Importantly, miR-200a was in-effective in Keap1-silenced (by shRNA) OB-6 cells. In the primary human osteoblasts, Keap1 silence by targeted-shRNA or miR-200a protected cells from dexamethasone. Significantly, miR-200a level was decreased in necrotic femoral head tissues, which was correlated with Keap1 mRNA upregulation. Together, miR-200a expression activates Nrf2 signaling and protects human osteoblasts from dexamethasone.


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