Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Tsai-Der Chuang

PROVIDER: E-GEOD-38817 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5.

Chuang Tsai-Der TD Panda Harekrushna H Luo Xiaoping X Chegini Nasser N

Endocrine-related cancer 20120722 4

MicroRNA-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 (LYO), benign uterine tumors with fibrotic characteristic. Using LYO and matched myometrium (MYO; n=76) from untreated and from patients exposed to hormonal therapies (GNRH agonist (GNRHa), Depo-Provera, and oral contraceptives), we found that miR-200c was expre ...[more]

PMID: 22685266

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Project description:miR-93/106b and their host gene minichromosome maintenance complex component 7 (MCM7) reside at chr7q22, a region frequently rearranged in leiomyomas. We explored the expression of miR-93/106b in leiomyoma and paired myometrium (N=62) from untreated and patients exposed to hormonal therapies (GnRHa, Depo-Provera and oral contraceptives) from African Americans and Caucasians, and their regulatory functions in isolated paired (N=15) leiomyoma and myometrial smooth muscle cells (LSMC and MSMC) and leiomyosarcoma cell line (SKLM-S1). At tissue level leiomyomas expressed significantly lower levels of miR-93 and elevated MCM7 as compared to myometrium with limited racial influence or hormonal exposure on their expression. Assessing the regulatory function of miR-93/106b through doxycycline-inducible lentiviral transduction in microarray analysis, tissue factor (F3) and IL-8 were identified as their possible targets. At tissue level leiomyomas expressed a significantly lower level of F3 and an elevated IL-8 which exhibited an inverse relationship with miR-93, but with limited racial or hormonal influences. Gain-of-function of miR-93/106b in LSMC, MSMC and SKLM-S1 dose-dependently repressed F3 and IL-8 through direct interactions with their respective 3M-bM-^@M-^YUTRs and indirectly through F3 repression inhibited IL8, CTGF and PAI-1 expression, confirmed by using siRNA silencing or factor Vlla (FVIIa) activation of F3, as well as reducing the rate of proliferation, while increasing caspase 3/7 activity. We concluded that differential expression of miR-93/106b and their direct and/or indirect regulatory functions on F3, IL-8, CTGF and PAI-1 expression, with key roles in inflammation and tissue turnover may be of significance in the outcome of leiomyoma growth and associated symptoms. Total RNA isolated from TF324 cells transfected with DOX-inducible lentiviral construct carrying miR-106b~25 cluster with and without Dox treatments for 6 days was subjected to gene expression profiling using Sentirx Beadchip Array HumanHT-12_v4.

Dataset Information

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

Publications

miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5.

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