MicroRNA-339-5p inhibits colorectal tumorigenesis through regulation of the MDM2/p53 signaling

// Cen Zhang 1,* , Juan Liu 1,* , Xiaolong Wang 1,2 , Rui Wu 1 , Meihua Lin 1 , Saurabh V. Laddha 3 , Qifeng Yang 1,2 , Chang S. Chan 3 and Zhaohui Feng 1 1 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA 2 Department of Breast Surgery, Qilu Hospital, Shandong University, Ji’nan, China 3 Center for Systems Biology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA * These auhors contributed equally to this work Correspondence: Zhaohui Feng, email: // Keywords : microRNA-339-5p; colorectal cancer; p53; migration; invasion; tumorigenesis Received : August 04, 2014 Accepted : August 20, 2014 Published : August 21, 2014 Abstract Tumor suppressor p53 plays a central role in tumor suppression. To ensure its proper function, the levels and activity of p53 are under a tight regulation in cells. MicroRNAs are short non-coding RNAs that play an important role in regulation of gene expression. Recently, microRNA-339-5p has been reported to be frequently down-regulated in colorectal cancer, and furthermore, its down-regulation is associated with poor prognosis in cancer patients, which strongly suggests a tumor suppressive function of microRNA-339-5p in colorectal cancer. In this study, we found that microRNA-339-5p directly represses the expression of MDM2, a key negative regulator of p53, through binding to MDM2 3’-UTR in colorectal cancer cells. Through the down-regulation of MDM2, microRNA-339-5p increases p53 protein levels and functions, including p53 transcriptional activity and p53-mediated apoptosis and senescence in response to stress. Furthermore, microRNA-339-5p inhibits the migration and invasion of colorectal cancer cells and the growth of colorectal xenograft tumors in a largely p53-dependent manner. Our results highlighted an important role of microRNA-339-5p in suppression of colorectal tumorigenesis, and also revealed that regulating the p53 function is an important mechanism for microRNA-339-5p in tumor suppression.