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Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression
Smith, Amber Rae Marquez, Rebecca T. Tsao, Wei-Chung Pathak, Surajit Roy, Alexandria Ping, Jie Wilkerson, Bailey Lan, Lan Meng, Wenjian Neufeld, Kristi L.
Smith, Amber Rae
Marquez, Rebecca T.
Tsao, Wei-Chung
Pathak, Surajit
Roy, Alexandria
Ping, Jie
Wilkerson, Bailey
Lan, Lan
Meng, Wenjian
Neufeld, Kristi L.
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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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Date
2015-03-30
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Impact Journals
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Keywords
Tumor-initiating cells, MicroRNAs, RNA-binding proteins, Colon cancer, Rectal cancer
Citation
Smith, Amber R., Rebecca T. Marquez, Wei-Chung Tsao, Surajit Pathak, Alexandria Roy, Jie Ping, Bailey Wilkerson, Lan Lan, Wenjian Meng, Kristi L. Neufeld, Xiao-Feng Sun, and Liang Xu. "Tumor Suppressive MicroRNA-137 Negatively Regulates Musashi-1 and Colorectal Cancer Progression." Oncotarget 6.14 (2015): 12558-2573. doi:10.18632/oncotarget.3726.