Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression |
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| Authors: | Amber R. Smith Rebecca T. Marquez Wei-Chung Tsao Surajit Pathak Alexandria Roy Jie Ping Bailey Wilkerson Lan Lan Wenjian Meng Kristi L. Neufeld Xiao-Feng Sun Liang Xu |
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| Affiliation: | 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 |
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| 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. |
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| Keywords: | tumor-initiating cells microRNAs RNA-binding proteins colon cancer rectal cancer |
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