Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes

Abstract

Oxidative stress is linked to increased risk of gastric cancer (GC). Recent reports have found that hsa-let-7g microRNA (miRNA) has properties of anti-tumor and resistance to damages induced by oxidized low-density lipoprotein (ox-LDL). Dysregulation of hsa-let-7g was present in GC in vivo and in vitro under exogenous stress. However, we didn’t know whether there are regulatory mechanisms of hsa-let-7g in GC under oxidative stress. This study was aimed at investigating the effects of hsa-let-7g microRNA (miRNA) on GC under oxidative stress. The results showed that H₂O₂ induced the increase of DNA damage response (DDR) genes (ATM, H2AX and Chk1) and downregulation of hsa-let-7g in GC cells. Further study confirmed Hsa-let-7g caused the apoptosis and loss of proliferation in GC cells exposed to H₂O₂ associated with repression of DDR system. Yet, we found let-7g didn’t target DDR genes (ATM, H2AX and Chk1) directly. In addition, data revealed hsa-let-7g miRNA increased the sensitivity of GC to X-rays involving in ATM regulation as well according to application of X-rays (another DDR inducer). In conclusion, Hsa-let-7g miRNA increased the sensitivity of GC to oxidative stress by repression activation of DDR indirectly. Let-7g improved the effects of X-rays on GC cells involving in DDR regulation as well.