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Retracted: Chemoresistance in gastric cancer is attributed to the overexpression of excision repair cross-complementing 1 (ERCC1) caused by microRNA-122 dysregulation
Authors:Ai-Ling Song  Lei Zhao  Yan-Wei Wang  Dong-Qiang He  Yu-Min Li
Affiliation:1. Department of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China

Ai-Ling Song and Lei Zhao contributed equally to this work.;2. Department of Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China

Abstract:MicroRNAs are deemed as key regulators of gene expression. In particular, the elevated expression of excision repair cross-complementing 1 (ERCC1) significantly reduced the effectiveness of gastric cancer treatment by cisplatin (CDDP)-based therapies. In this paper, qRT-PCR and western blot were adopted to measure miR-122 and ERCC1 messenger RNA (mRNA) expression in all samples. Luciferase assay was carried out to verify the role of ERCC1 as a target of miR-122. The CCK-8 assay was carried out to study the effect of ERCC1 and miR-122 on cell survival and apoptosis. The results demonstrated that miR-122 expression was reduced in cisplatin-resistant gastric cancer. Using bioinformatic analysis, miR-122 was shown to target the 3′-UTR of human ERCC1. A dual-luciferase assay demonstrated that miR-122 downregulated ERCC1 expression, while the mutations in ERCC1 3′-UTR abolished its interaction with miR-122. Transfection of miR-122 mimics decreased the levels of ERCC1 mRNA and protein expression, while the transfection of miR-122 inhibitors increased the levels of both ERCC1 mRNA and protein expression. Furthermore, we found that overexpressed miR-122 promoted the proliferation of MKN74 cells and reduced their apoptotic by targeting ERCC1. In addition, the levels of miR-122 and ERCC1 were negatively correlated in gastric cancer samples. In summary, the reduced miR-122 expression may play an essential role in the induction of cisplatin-resistance by increasing ERCC1 expression.
Keywords:apoptosis  chemoresistance  ERCC1  gastric cancer  microRNA-122  proliferation
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