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Biochem Biophys Res Commun. 2019 May 9. pii: S0006-291X(19)30894-0. doi: 10.1016/j.bbrc.2019.05.026. [Epub ahead of print]

microRNA-4532 inhibition protects human lens epithelial cells from ultra-violet-induced oxidative injury via activating SIRT6-Nrf2 signaling.

Author information

1
The Fourth School of Clinical Medicine, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, 210029, China.
2
The Fourth School of Clinical Medicine, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, 210029, China. Electronic address: Jqin710@vip.sina.com.

Abstract

Ultra-violet radiation (UVR) can induce significant oxidative injury to human lens epithelial cells (HLECs). Sirtuin 6 (SIRT6) is shown to directly bind to Nrf2, essential for Nrf2 signaling activation. In the present study, we show that microRNA-4532 (miR-4532) targets SIRT6 to regulate Nrf2 signaling in HLECs. Ectopic overexpression of miR-4532 in HLECs decreased SIRT6 3'-UTR activity, causing SIRT6 downregulation and Nrf2 signaling inhibition. Conversely, miR-4532 inhibition, by a lentiviral construct, enhanced SIRT6 3'-UTR activity, SIRT6 expression and Nrf2 signaling activation. Functional studies show that UVR-induced cytotoxicity and apoptosis in HLECs were potentiated by miR-4532 overexpression, Nrf2 depletion or SIRT6 shRNA. Conversely, miR-4532 inhibition or ectopic SIRT6 overexpression attenuated UVR-induced oxidative injury in HLECs. Importantly, miR-4532 overexpression or inhibition was ineffective in SIRT6-KO or Nrf2-KO HLECs. Taken together, the results show that inhibition of miR-4532 protects HLECs from UVR-induced oxidative injury via activation of SIRT6-Nrf2 pathway. Targeting the miR-4532-SIRT6-Nrf2 pathway could be a novel strategy to protect HLECs from UVR and possible other oxidative stresses.

KEYWORDS:

Human lens epithelial cells; SIRT6 and Nrf2; Ultra-violet radiation; microRNA-4532

PMID:
31079921
DOI:
10.1016/j.bbrc.2019.05.026

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