Open AccessDual tumor‐suppressors miR‐139‐5p and miR‐139‐3p targeting matrix metalloprotease 11 in bladder cancer
Author(s) -
Yonemori Masaya,
Seki Naohiko,
Yoshino Hirofumi,
Matsushita Ryosuke,
Miyamoto Kazutaka,
Nakagawa Masayuki,
Enokida Hideki
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13002
Subject(s) - rna , small interfering rna , gene expression , cancer research , biology , microrna , rna interference , bladder cancer , microbiology and biotechnology , gene , cancer , genetics
Our recent study of the micro RNA (mi RNA ) expression signature of bladder cancer ( BC ) by deep‐sequencing revealed that two mi RNA , micro RNA ‐139‐5p / micro RNA ‐139‐3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these mi RNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature mi RNA or small interfering RNA (si RNA ). Genome‐wide gene expression analysis, in silico analysis and dual‐luciferase reporter assays were applied to identify mi RNA targets. The associations between the expression of mi RNA 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 ( MMP 11 ) was identified as a direct target of miR‐139‐5p and miR‐139‐3p . Kaplan–Meier survival curves showed that higher expression of MMP 11 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. MMP 11 was directly regulated by these mi RNA and might be a good prognostic marker for survival of BC patients.