The long non-coding RNA MALAT1 activates Nrf2 signaling to protect human umbilical vein endothelial cells from hydrogen peroxide

Abstract

The potential effect of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) against hydrogen peroxide (H₂O₂)-induced oxidative injury in endothelial cells was tested. We show that forced-expression of MALAT1 using a lentiviral vector ("LV-MALAT1") significantly attenuated H₂O₂-induced death and apoptosis of human umbilical vein endothelial cells (HUVECs). Conversely, knocking down of MALAT1 by targeted siRNA exacerbated H₂O₂-induced HUVEC injury. For the mechanism study, we show that LV-MALAT1 induced Keap1 downregulation, leading to nuclear-factor-E2-related factor 2 (Nrf2) stabilization and activation. Critically, Nrf2 shRNA almost completely abolished LV-MALAT1-mediated HUVEC protection against H₂O₂. Significantly, H₂O₂-induced oxidative stress, lipid peroxidation and DNA damages in HUVECs were attenuated by LV-MALAT1, but were intensified with MALAT1 siRNA. In summary, we identified a novel signaling axis involving MALAT1, Keap1 and Nrf2, which in turn protects HUVECs from oxidative injury.

Keywords: HUVECs; Keap1; MALAT1; Nrf2; Oxidative stress.