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

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

doi:10.18632/oncotarget.3726

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Research Papers:

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

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 and Liang Xu _

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Oncotarget. 2015; 6:12558-12573. https://doi.org/10.18632/oncotarget.3726

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Abstract

Amber R. Smith1, Rebecca T. Marquez1, Wei-Chung Tsao1, Surajit Pathak3, Alexandria Roy1, Jie Ping3, Bailey Wilkerson1, Lan Lan1, Wenjian Meng3, Kristi L. Neufeld1,4, Xiao-Feng Sun3 and Liang Xu1,2

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.

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Research Papers:

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

Abstract