A systematic evaluation of miRNA:mRNA interactions involved in the migration and invasion of breast cancer cells

Journal of Translational Medicine

Huidong Shi³  LesleyAnn Hawthorn¹  Shuang Huang³  Lirong Pei²  Jimei Liu²  Nikki Harvel²  James M Wilson²  Daya Luo² 

[1] Department of Pathology, Georgia Health Sciences University, Augusta, GA, USA;GHSU Cancer Center, Georgia Health Sciences University, Augusta, GA, USA;Department of Biochemistry and Molecular Biology, Georgia Health Sciences University, Augusta, GA, USA

关键词: Invasion;    Migration;    MicroRNA target genes;    Breast cancer;   

Others  :  827991
DOI  :  10.1186/1479-5876-11-57

 received in 2012-10-23, accepted in 2013-02-05,  发布年份 2013

【 摘 要 】

In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the invasiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in invasive cell lines when compared to normal and less invasive cell lines. Transfection of miR-200c, miR-205, and miR-375 mimics into MDA-MB-231 cells led to the inhibition of in vitro cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that miR-200c plays a pivotal role in regulating the invasiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer invasiveness and ultimately lead to the identification of novel biomarkers associated with prognosis.

【 授权许可】

   
2013 Luo et al; licensee BioMed Central Ltd.

【 图 表 】

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