Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression.
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.
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Amber R
AR
Smith
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Rebecca T
RT
Marquez
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Wei-Chung
WC
Tsao
Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Surajit
S
Pathak
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Alexandria
A
Roy
Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Jie
J
Ping
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Bailey
B
Wilkerson
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.
Lan
L
Lan
Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Wenjian
W
Meng
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.|Department of Cancer Biology, The Kansas University Medical Center, Kansas City, KS, USA.
Kristi L
KL
Neufeld
Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Xiao-Feng
XF
Sun
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.|Department of Radiation Oncology, The Kansas University Medical Center, Kansas City, KS, USA.
Liang
L
Xu
D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
C545567:MIRN137 microRNA, human; C491297:MSI1 protein, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins
RNA-binding proteins; colon cancer; microRNAs; rectal cancer; tumor-initiating cells