RRC ID 47712
Author Yonemori M, Seki N, Yoshino H, Matsushita R, Miyamoto K, Nakagawa M, Enokida H.
Title Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.
Journal Cancer Sci
Abstract Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.
Volume 107(9)
Pages 1233-42
Published 2016-9-1
DOI 10.1111/cas.13002
PMID 27355528
PMC PMC5021030
MeSH Cell Line, Tumor Cell Movement / genetics Cell Proliferation Female Gene Expression Gene Expression Profiling Gene Expression Regulation, Neoplastic* Gene Knockdown Techniques Genes, Reporter Humans Immunohistochemistry Male Matrix Metalloproteinase 11 / genetics* MicroRNAs / genetics* Prognosis RNA Interference* RNA, Messenger / genetics Transfection Urinary Bladder Neoplasms / genetics* Urinary Bladder Neoplasms / mortality Urinary Bladder Neoplasms / pathology
IF 4.966
Times Cited 75
DNA material MMP11-miR-139-5P wild (RDB14547) MMP11-miR-139-5P del (RDB14548) MMP11-miR-139-3P wild (RDB14549) MMP11-miR-139-3P del (RDB14550).