title: 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-7 g microRNA (miRNA) has properties of anti-tumor and resistance to damages induced by oxidized low-density lipoprotein (ox-LDL). Dysregulation of hsa-let-7 g 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-7 g in GC under oxidative stress. This study was aimed at investigating the effects of hsa-let-7 g 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-7 g in GC cells. Further study confirmed Hsa-let-7 g caused the apoptosis and loss of proliferation in GC cells exposed to H2O2 associated with repression of DDR system. Yet, we found let-7 g didn't target DDR genes (ATM, H2AX and Chk1) directly. In addition, data revealed hsa-let-7 g 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-7 g miRNA increased the sensitivity of GC to oxidative stress by repression activation of DDR indirectly. Let-7 g improved the effects of X-rays on GC cells involving in DDR regulation as well.
authors.affiliation: Department of Gastroenterology and Hepatology, the Affiliated Hospital of Inner Mongolia Medical University.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Hu
authors.forename: Xuanzhong
authors.initials: X
authors.lastname: Zhao
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jin
authors.forename: Mingxing
authors.initials: M
authors.lastname: Hou
mesh_terms: D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000071877:Checkpoint Kinase 1; D004249:DNA Damage / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones; D006801:Humans; D008077:Lipoproteins, LDL; D035683:MicroRNAs / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics*; D011494:Protein Kinases; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C099252:oxidized low density lipoprotein; D011494:Protein Kinases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1