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

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 signal...

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Veröffentlicht in:Biochemical and biophysical research communications 2019-06, Vol.514 (3), p.777-784
Hauptverfasser: Sun, Guang-li, Huang, Dan, Li, Ke-ran, Jiang, Qin
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Sprache:eng
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Zusammenfassung: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. •MiR-4532 targets SIRT6 and inhibits Nrf2 signaling in human lens epithelial cells (HLECs).•MiR-4532 inhibition enhances SIRT6 expression and Nrf2 signaling activation in HLECs.•UVR-induced oxidative injury in HLECs is alleviated by miR-4532 inhibition.•SIRT6 and Nrf2 signaling are the primary targets of miR-4532 in HLECs.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.05.026