期刊
DNA REPAIR
卷 12, 期 9, 页码 741-750出版社
ELSEVIER
DOI: 10.1016/j.dnarep.2013.06.002
关键词
Gastric cancer; miR-375; P53; Ionizing radiation; Etoposide
资金
- National Bio-Tech 863 [2012AA02A203, 2012AA02A504]
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. (c) 2013 Elsevier B.V. All rights reserved.
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