MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1

Molecular Cancer

Research

Jamboor K Vishwanatha¹  Smrithi Rajendiran¹  Subhamoy Dasgupta²  Rhonda K Roby³  Richard J Hare⁴  Anil V Parwani⁵ 

[1] From the Department of Molecular and Medical Genetics and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, 76107, Fort Worth, TX, USA;From the Department of Molecular and Medical Genetics and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, 76107, Fort Worth, TX, USA;Department of Molecular and Cellular Biology, Baylor College of Medicine, 77030, Houston, TX, USA;From the Department of Molecular and Medical Genetics and Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, 76107, Fort Worth, TX, USA;J. Craig Venter Institute, 92037, LaJolla, CA, USA;From the Department of Pathology, Plaza Medical Center, 76104, Fort Worth, TX, USA;From the Department of Pathology, UPMC Shadyside Hospital, 15232, Pittsburgh, PA, USA;

关键词: Migration;    Invasion;    Post-transcription regulation;    Prostate cancer;    MicroRNA;    MIEN1;    miRNA-940;   

DOI  :  10.1186/1476-4598-13-250

 received in 2014-06-12, accepted in 2014-10-23,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies.MethodsThe miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3′UTR, cells were transfected with the oligomiRs and plasmids, respectively.ResultsA novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET).ConclusionsThese results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer.

【 授权许可】

Unknown   
© Rajendiran et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.