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Genome-wide miRNA profile of MCF7 cells overexpressing wild-type and mutant miR-222

ABSTRACT: MCF7 cells were infected with retrovirus to overexpress wild-type and mutant miR-222

ORGANISM(S): Homo sapiens

PROVIDER: GSE64363 | GEO | 2015/02/05

SECONDARY ACCESSION(S): PRJNA270829

REPOSITORIES: GEO

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Genome-wide miRNA profile of MCF7 cells overexpressing wild-type and mutant miR-222

Project description:MCF7 cells were infected with retrovirus to overexpress wild-type and mutant miR-222 Measure miRNA expression level in MCF7 cells after overexpressing wild-type and mutant miR-222

2015-02-05 | E-GEOD-64363 | biostudies-arrayexpress

Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells

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Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells

Project description:Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment. Fulvestrant-resistant breast cancer cells MCF7-FR (originated from drug-sentitive breast cancer model cell line MCF7) were transient-transfected by antigomirs targeting miR221 or miR222 (i.e. si221, si222). All three cell lines, MCF7-FR, siR221, siRNA222 were subjected to gene expression profiling.

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222

Project description:222

| PRJEB34284 | ENA

Gene expression profiling of MCF10A (miR-221/222 vs control)

Project description:Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222

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Gene expression profiling of MCF10A (miR-221/222 vs control)

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miR-222 regulation of the tolerized LPS response

Project description:The purpose of this study is to determine the effect miR-221/222 have on LPS-induced gene expression in macrophages.

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miR-221/222 drive synovial fibroblast expansion and pathogenesis of TNF-mediated arthritis

Project description:MicroRNAs (miRNAs) constitute fine tuners of gene expression and are implicated in a variety of diseases spanning from inflammation to cancer. miRNA expression is deregulated in rheumatoid arthritis (RA), however, their specific role in key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. We have shown in the past that the expression of the miR-221/222 cluster is upregulated in RA SFs. Here, we demonstrate that miR-221/222 activation is downstream of major inflammatory cytokines, such as TNF and IL-1β, which promote miR-221/222 expression independently. miR-221/222 expression in SFs from the huTNFtg mouse model of arthritis correlates with disease progression. Targeted transgenic overexpression of miR-221/222 in SFs of the huTNFtg mouse model led to further expansion of synovial fibroblasts and disease exacerbation. miR-221/222 overexpression altered the transcriptional profile of SFs igniting pathways involved in cell cycle progression and ECM regulation. Validated targets of miR-221/222 included p27 and p57 cell cycle inhibitors, as well as Smarca1 (a chromatin remodeling component). In contrast, complete genetic ablation of miR-221/222 in arthritic mice led to decreased proliferation of fibroblasts, reduced synovial expansion and attenuated disease. scATAC-seq data analysis revealed increased miR-221/222 gene activity in the pathogenic and activated clusters of the intermediate and lining compartment. Taken together, our results establish an SF-specific pathogenic role of the miR-221/222 cluster in arthritis and suggest that its therapeutic targeting in specific subpopulations should inform the design of novel fibroblast-targeted therapies for human disease.

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