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.
Source: A systematic evaluation of miRNA:mRNA interactions
involved in the migration and invasion of breast cancer cells. Luo D, Wilson JM, Harvel N, Liu J, Pei L,
Huang S, Hawthorn L, Shi H (hshi@georgiahealth.edu).
J Transl Med. 2013 Mar 5;11:57.
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