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

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  • Hu Haiqing
    Department of Gastroenterology and Hepatology, the Affiliated Hospital of Inner Mongolia Medical University
  • Zhao Xuanzhong
    Gastrointestinal surgery, the Affiliated Hospital of Inner Mongolia Medical University
  • Jin Zhao
    Gastrointestinal surgery, the Affiliated Hospital of Inner Mongolia Medical University
  • Hou Mingxing
    Gastrointestinal surgery, the Affiliated Hospital of Inner Mongolia Medical University

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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.

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