miRNA-7-5p inhibits melanoma cell migration and invasion

被引:80
作者
Giles, Keith M. [1 ,2 ]
Brown, Rikki A. M. [1 ,2 ]
Epis, Michael R. [1 ,2 ]
Kalinowski, Felicity C. [1 ,2 ]
Leedman, Peter J. [1 ,2 ,3 ]
机构
[1] Western Australian Inst Med Res, Lab Canc Med, Perth, WA 6000, Australia
[2] Univ Western Australia, Med Res Ctr, Perth, WA 6000, Australia
[3] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6008, Australia
基金
英国医学研究理事会;
关键词
microRNA; Melanoma; Migration; Invasion; Metastasis; Signaling; GROWTH-FACTOR RECEPTOR; HUMAN CANCER-CELLS; GENE-EXPRESSION; MICRORNA REGULATION; GLIOBLASTOMA; PROGRESSION; REGULATORS; THERAPY; TARGETS; KINASE;
D O I
10.1016/j.bbrc.2012.11.086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aberrant expression of microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been implicated in the development and progression of melanoma. However, the precise mechanistic role of many of these miRNAs remains unclear. We have investigated the functional role of miR-7-5p in melanoma, and demonstrate that miR-7-5p expression is reduced in metastatic melanoma-derived cell lines compared with primary melanoma cells, and that when ectopically expressed miR-7-5p significantly inhibits melanoma cell migration and invasion. Additionally, we report that insulin receptor substrate-2 (IRS-2) is a target of miR-7-5p in melanoma cells, and using RNA interference (RNAi) we provide evidence that IRS-2 activates protein kinase B (Akt), and promotes melanoma cell migration. Thus, miR-7-5p may represent a novel tumor suppressor miRNA in melanoma, acting at least in part via its inhibition of IRS-2 expression and oncogenic Akt signaling. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:706 / 710
页数:5
相关论文
共 35 条
[1]   The Promise of MicroRNA Replacement Therapy [J].
Bader, Andreas G. ;
Brown, David ;
Winkler, Matthew .
CANCER RESEARCH, 2010, 70 (18) :7027-7030
[2]   MicroRNA regulation of melanoma progression [J].
Bonazzi, Vanessa F. ;
Stark, Mitchell S. ;
Hayward, Nicholas K. .
MELANOMA RESEARCH, 2012, 22 (02) :101-113
[3]   Regulation of mRNA Translation and Stability by microRNAs [J].
Fabian, Marc Robert ;
Sonenberg, Nahum ;
Filipowicz, Witold .
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 79, 2010, 79 :351-379
[4]   NERVE GROWTH-FACTOR RECEPTORS ON HUMAN MELANOMA CELLS IN CULTURE [J].
FABRICANT, RN ;
DELARCO, JE ;
TODARO, GJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (02) :565-569
[5]   MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma [J].
Fang, YuXiang ;
Xue, Jing-Lun ;
Shen, Qi ;
Chen, Jinzhong ;
Tian, Ling .
HEPATOLOGY, 2012, 55 (06) :1852-1862
[6]   Targeting Metastatic Melanoma [J].
Flaherty, Keith T. .
ANNUAL REVIEW OF MEDICINE, VOL 63, 2012, 63 :171-183
[7]   microRNAs: Master Regulators as Potential Therapeutics in Cancer [J].
Garofalo, Michela ;
Croce, Carlo M. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011, 2011, 51 :25-43
[8]   IN-VITRO CULTIVATION OF HUMAN TUMORS - ESTABLISHMENT OF CELL LINES DERIVED FROM A SERIES OF SOLID TUMORS [J].
GIARD, DJ ;
AARONSON, SA ;
TODARO, GJ ;
ARNSTEIN, P ;
KERSEY, JH ;
DOSIK, H ;
PARKS, WP .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1973, 51 (05) :1417-1423
[9]  
Giles KM, 2011, METHODS MOL BIOL, V676, P147, DOI 10.1007/978-1-60761-863-8_11
[10]  
HERLYN M, 1985, JNCI-J NATL CANCER I, V74, P283