A systematic evaluation of miRNA

MRNA interactions involved in the migration and invasion of breast cancer cells

Daya Luo, James M. Wilson, Nikki Harvel, Jimei Liu, Lirong Pei, Shuang Huang, Lesleyann Hawthorn, Huidong Shi

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number57
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
StatePublished - Mar 5 2013

Fingerprint

MicroRNAs
Cells
Breast Neoplasms
Genes
Cell Line
Messenger RNA
Tissue Array Analysis
Tissue
Biomarkers
Bioinformatics
Microarrays
Computational Biology
Cell Movement
Transfection
Tumors
Assays
Neoplasms

Keywords

  • Breast cancer
  • Invasion
  • MicroRNA target genes
  • Migration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A systematic evaluation of miRNA : MRNA interactions involved in the migration and invasion of breast cancer cells. / Luo, Daya; Wilson, James M.; Harvel, Nikki; Liu, Jimei; Pei, Lirong; Huang, Shuang; Hawthorn, Lesleyann; Shi, Huidong.

In: Journal of Translational Medicine, Vol. 11, No. 1, 57, 05.03.2013.

Research output: Contribution to journalArticle

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