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MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell.

ABSTRACT: MicroRNA-7 (miR-7) is a non-coding RNA of 23-nucleotides that has been shown to act as a tumor suppressor in various cancers including breast cancer. Although there have been copious studies on the action mechanisms of miR-7, little is known about how the miR is controlled in the mammary cell. In this study, we performed a genome-wide expression analysis in miR-7-transfected MCF-10A breast cell line to explore the upstream regulators of miR-7. Analysis of the dysregulated target gene pool predicted hepatocyte growth factor (HGF) as the most plausible upstream regulator of miR-7. MiR-7 was upregulated in MCF-10A cells by HGF, and subsequently downregulated upon treatment with siRNA against HGF. However, the expression of HGF did not significantly change through either an upregulation or downregulation of miR-7 expression, suggesting that HGF acts upstream of miR-7. In addition, the target genes of miR-7, such as EGFR, KLF4, FAK, PAK1 and SET8, which are all known oncogenes, were downregulated in HGF-treated MCF-10A; in contrast, knocking down HGF recovered their expression. These results indicate that miR-7 mediates the activity of HGF to suppress oncogenic proteins, which inhibits the development of normal cells, at least MCF-10A, into cancerous cells.

SUBMITTER: Jeong D

PROVIDER: S-EPMC5684415 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell.

Jeong Dawoon D Ham Juyeon J Park Sungbin S Lee Seungyeon S Lee Hyunkyung H Kang Han-Sung HS Kim Sun Jung SJ

Scientific reports 20171113 1

MicroRNA-7 (miR-7) is a non-coding RNA of 23-nucleotides that has been shown to act as a tumor suppressor in various cancers including breast cancer. Although there have been copious studies on the action mechanisms of miR-7, little is known about how the miR is controlled in the mammary cell. In this study, we performed a genome-wide expression analysis in miR-7-transfected MCF-10A breast cell line to explore the upstream regulators of miR-7. Analysis of the dysregulated target gene pool predic ...[more]

PMID: 29133945

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Project description:OBJECTIVE:This study investigated the role of microRNAs generated from adipose tissue macrophages (ATMs) during adipose tissue remodeling induced by pharmacological and nutritional stimuli. METHODS:Macrophage-specific Dicer knockout (KO) mice were used to determine the roles of microRNA generated in macrophages in adipose tissue remodeling induced by the β3-adrenergic receptor agonist CL316,243 (CL). RNA-seq was performed to characterize microRNA and mRNA expression profiles in isolated macrophages and PDGFRα+ adipocyte stem cells (ASCs). The role of miR-10a-5p was further investigated in cell culture, and in adipose tissue remodeling induced by CL treatment and high fat feeding. RESULTS:Macrophage-specific deletion of Dicer elevated pro-inflammatory gene expression and prevented CL-induced de novo beige adipogenesis in gonadal white adipose tissue (gWAT). Co-culture of ASCs with ATMs of wild type mice promoted brown adipocyte gene expression upon differentiation, but co-culture with ATMs of Dicer KO mice did not. Bioinformatic analysis of RNA expression profiles identified miR-10a-5p as a potential regulator of inflammation and differentiation in ATMs and ASCs, respectively. CL treatment increased levels of miR-10a-5p in ATMs and ASCs in gWAT. Interestingly, CL treatment elevated levels of pre-mir-10a in ATMs but not in ASCs, suggesting possible transfer from ATMs to ASCs. Elevating miR-10a-5p levels inhibited proinflammatory gene expression in cultured RAW 264.7 macrophages and promoted the differentiation of C3H10T1/2 cells into brown adipocytes. Furthermore, treatment with a miR-10a-5p mimic in vivo rescued CL-induced beige adipogenesis in Dicer KO mice. High fat feeding reduced miR-10a-5p levels in ATMs of gWAT, and treatment of mice with a miR-10a-5p mimic suppressed pro-inflammatory responses, promoted the appearance of new white adipocytes in gWAT, and improved systemic glucose tolerance. CONCLUSIONS:These results demonstrate an important role of macrophage-generated microRNAs in adipogenic niches and identify miR-10a-5p as a key regulator that reduces adipose tissue inflammation and promotes therapeutic adipogenesis.

Dataset Information

MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell.

Publications

MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell.

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