miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells.

MicroRNAs (miRNAs) offer a new approach for molecular classification and individual therapy of human cancer due to their regulation of oncogenic pathways. In a previous report, elevated miR-375 was found in recurring gastric cancer, and it was predicted that miR-375 may be a regulator of p53 gene. However, its biological role and mechanism of actions remain unknown. In this study, we characterized the expression level of miR-375 in gastric cancer cell lines--BGC823, MGC803, SGC7901, AGS, N87, MKN45--using RT-PCR. We found that exogenous expression of miR-375 promoted the growth of AGS cells in both liquid and soft agar media. In agreement with the previous report, overexpression of miR-375 in AGS cells reduced the p53 protein expression level. A luciferase assay demonstrated that miR-375 down-regulated p53 expression through an interaction with the 3' UTR region of p53. In addition, the expression of miR-375 desensitizes cells to ionizing radiation and etoposide. Flow cytometry analyses showed that miR-375 abrogated the cell cycle arrest and apoptosis after DNA damage. These results demonstrate that miR-375 targets p53 to regulate the response to ionizing radiation and etoposide treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Citation

Yixuan Liu, Rui Xing, Xiaodong Zhang, Weiwei Dong, Jingyu Zhang, Zhi Yan, Wenmei Li, Jiantao Cui, Youyong Lu. miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA repair. 2013 Sep;12(9):741-50

PMID: 23835407

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