miR-200c is Aberrantly Expressed in Leiomyomas in Ethnic-Dependent Manner and Targets ZEBs, VEGFA, TIMP2 and FBLN5

mircoRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas, benign uterine tumors with fibrotic characteristic. Gain-of function of miR-200c in isolated leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1) repressed ZEB1/ZEB2 mRNAs and proteins, with concurrent increase in E-cadherin (CDH1) and reduction in vimentin expression, phenotypic alteration and inhibition of MSMC and LSMC proliferation. We further validated TIMP2, FBLN5 and VEGFA as direct targets of miR-200c through interaction with their respective 3’UTRs, and other genes as determined by microarray analysis. Total RNA isolated from MSMC and LSMC following gain-of function of miR-200c was subjected to gene expression profiling using HumanHT-12 v4 Expression BeadChip (Illumina, Inc. San Diego, CA) consists of 47,000 oligonucleotide probe sets representing 28,688 transcripts.