MicroRNA‐365 Targets Nrf2 To Enhance Erastin-Induced Ferroptosis In Gastric Cancer Cells

Abstract

Abstract Gastric cancer is globally recognized as a significant malignancy and a leading cause of cancer mortality. Ferroptosis, as a new form of regulated cell death, is attracting increasing attention in worldwide. As knows that, MicroRNA-365 (miR-365) has been implicated in the carcinogenesis of gastric cancer, but its role in ferroptosis remains elusive. The aim of our study is to clarify how miR-365 regulate ferroptosis in gastric cancer cells. Erastin is regarded as a ferroptosis inducer, our study found that with over-expression of miR-365 mimics also could enhance erastin-induced ferroptosis in gastric cancer cells. Additionally, miR-365 overexpression further upregulated the levels of MDA, Fe2+, and ROS in gastric cancer cells exposed to erastin, while antioxidant GSH levels were further downregulated, suggestive of enhanced lipid oxidation in gastric cancer cells upon erastin treatment through miR-365 overexpression. Notably, Nrf2 participated in the ferroptosis of cancer cells, as its upregulation was observed in gastric cancer cells after erastin exposure. qRT-PCR and Western blot analysis has shown that after exposed with erastin, the transcription and translation levels of Nrf2 in SGC-7901 and MGC-803 cells was increased. Overexpression of miR-365 in these cells attenuated the induction of Nrf2 by anti-aging drugs. The luciferase reporter assays data providing the evidence that miR-365 could directly target Nrf2. In conclusion, our study demonstrates that MicroRNA-365 could directly targets Nrf2. And its expression enhance ferroptosis induced by erastin in gastric cancer cells. This may provide a new target for therapy of gastric cancer regarding ferroptosis.