miR-34a inhibits migration and invasion by regulating the SIRT1/p53 pathway in human SW480 cells

作者：Ming-Guang Lai, Gang Du, Ruiyue Shi, Jun Yao, Genhua Yang, Wei Yue, Dingguo Zhang, Zhenglei Xu, Ru Zhang, Yingxue Li, Zicheng Li, Lisheng Wang · 发表于：Molecular Medicine Reports · 年份：2015 · DOI：10.3892/mmr.2015.3182 · 被引用次数：57 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、RNA Research and Splicing

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.