Smith Amber R, Marquez Rebecca T, Tsao Wei-Chung, Pathak Surajit, Roy Alexandria, Ping Jie, Wilkerson Bailey, Lan Lan, Meng Wenjian, Neufeld Kristi L, Sun Xiao-Feng, Xu Liang
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Oncotarget. 2015 May 20;6(14):12558-73. doi: 10.18632/oncotarget.3726.
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.
干细胞标志物Musashi-1（MSI1）在多种癌症类型中过度表达；然而，MSI1过度表达所涉及的分子机制尚未完全明确。我们研究了MSI1的微小RNA（miRNA）调控及其在结直肠癌中的作用。通过免疫印迹和荧光素酶报告基因检测，发现微小RNA miR-137是靶向MSI1的微小RNA。在79%的原发性直肠肿瘤（n=146）中发现MSI1蛋白高表达，而与配对的正常黏膜样本相比，84%的直肠肿瘤组织（n=68）中miR-137表达降低。除了降低MSI1蛋白水平外，miR-137的外源性表达还抑制了结肠癌细胞的生长、集落形成和肿瘤球生长。最后，体内研究表明，miR-137的诱导可降低人结肠癌异种移植瘤的生长。我们的结果表明，miR-137在结直肠癌中作为一种肿瘤抑制性miRNA发挥作用，并对致癌性MSI1起负调控作用。
