期刊
MOLECULAR MEDICINE REPORTS
卷 11, 期 5, 页码 3301-3307出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.3182
关键词
microRNA-34a; SIRT1; p53; SW480 cells
资金
- Natural Science Foundation of Guangdong Province [10151802001000002]
- Science and Technology Planning Project of Shenzhen [201201013]
- Technical Research and Development Project of Shenzhen [JCYJ20130402092657774]
MicroRNA-34a (miR-34a) is a direct transcriptional target of p53, and is downregulated in several different types of cancer. However, the underlying mechanism of the miR-34a effects in colorectal cancer is not well understood. In this study, we explored the role of miR-34a in cell invasion, migration, and apoptosis. Transient overexpression of miR-34a in SW480 cells caused a severe decrease in cell migration and invasion (both, p<0.05) compared to the control groups. Combining miR-34a transfection with 5-fluorouracil (5-FU) treatment further enhanced the inhibition in SW480 cell migration and invasion (both, p<0.05) compared to 5-FU treatment alone. These cellular changes were associated with upregulation of acetylated-p53 (ac-p53) and p21 and downregulation of sirtuin 1 (SIRT1). These data demonstrate that miR-34a regulates the expression of a number of critical proteins involved in apoptosis, proliferation and the response to chemotherapy. In summary, miR-34a increases the sensitivity of colon cancer cells to 5-FU treatment through specific regulation of the SIRT1/p53 pathway.
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