Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression

// Amber R. Smith 1 , Rebecca T. Marquez 1 , Wei-Chung Tsao 1 , Surajit Pathak 3 , Alexandria Roy 1 , Jie Ping 3 , Bailey Wilkerson 1 , Lan Lan 1 , Wenjian Meng 3 , Kristi L. Neufeld 1,4 , Xiao-Feng Sun 3 and Liang Xu 1,2 1 Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA 2 Department of Radiation Oncology, The Kansas University Medical Center, Kansas City, KS, USA 3 Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden 4 Department of Cancer Biology, The Kansas University Medical Center, Kansas City, KS, USA Correspondence to: Liang Xu, email: // Keywords : tumor-initiating cells, microRNAs, RNA-binding proteins, colon cancer, rectal cancer Received : September 25, 2014 Accepted : March 04, 2015 Published : May 20, 2015 Abstract Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.