Dataset Information

MiR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.

ABSTRACT: Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and RNF11 by dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR) in cardiomyocytes. We further explored the function of miR-200a-5p and observed that overexpression of miR-200a-5p spark the receptor interacting serine/threonine kinase 3 (RIP3)-dependent necroptosis in vivo and in vitro. To understand whether miR-200a-5p and RNF11 are involved in the RIP3-dependent necroptosis pathway, we presumed that oxidative stress, inflammation response and the mitogen-activated protein kinase (MAPK) pathway might trigger necroptosis. Interestingly, necroptosis trigger, z-VAD-fmk, failed to induce necroptosis but enhanced cell survival against necrosis in cardiomyocytes with knockdown of miR-200a-5p. Our present study provides a new insight that the modulation of miR-200a-5p and its target gene might block necroptosis in the heart, revealing a novel myocardial necrosis regulation model in heart disease.

SUBMITTER: Yang T

PROVIDER: S-EPMC5975215 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.

Yang Tianshu T Cao Changyu C Yang Jie J Liu Tianqi T Lei Xin Gen XG Zhang Ziwei Z Xu Shiwen S

Redox biology 20171208

Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and ...[more]

PMID: 29248830

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Project description:Tumor escape is often associated with abnormalities in the surface expression of the human leukocyte antigen class I (HLA-I) antigens thereby limiting CD8+ cytotoxic T cell responses. This impaired HLA-I surface expression can be mediated by deficient expression of components of the antigen processing and presentation machinery (APM) due to epigenetic, transcriptional and/or post-transcriptional processes. Since a discordant mRNA and protein expression pattern of APM components including the peptide transporter associated with antigen processing 1 (TAP1) has been frequently described in tumors of distinct origin, a post-transcriptional control of APM components caused by microRNAs (miR) was suggested. Using an in silico approach, miR-200a-5p has been identified as a candidate miR binding to the 3' untranslated region (UTR) of TAP1. Luciferase reporter assays demonstrated a specific binding of miR-200a-5p to the TAP1 3'-UTR. Furthermore, the miR-200a-5p expression is inversely correlated with the TAP1 protein expression in HEK293T cells and in a panel of melanoma cell lines as well as in primary melanoma lesions. High levels of miR-200a-5p expression were associated with a shorter overall survival of melanoma patients. Overexpression of miR-200a-5p reduced TAP1 levels, which was accompanied by a decreased HLA-I surface expression and an enhanced NK cell sensitivity of melanoma cells. These data show for the first time a miR-mediated control of the peptide transporter subunit TAP1 in melanoma thereby leading to a reduced HLA-I surface expression accompanied by an altered immune recognition and reduced patients' survival.AbbreviationsAb: antibody; ACTB: β-actin; APM: antigen processing and presentation machinery; ATCC: American tissue culture collection; β2-m: β2-microglobulin; BSA: bovine serum albumin; CTL: cytotoxic T lymphocyte; FCS: fetal calf serum; FFL: firefly luciferase; FFPE: formalin-fixed paraffin-embedded; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: heavy chain; HLA: human leukocyte antigen; HLA-I: HLA class I; HRP: horseradish peroxidase; IFN: interferon; im-miR: immune modulatory miRNA; LMP: low molecular weight protein; luc: luciferase; MFI: mean fluorescence intensity; MHC: major histocompatibility complex; miR: microRNA; NC: negative control; NK: natural killer; NSCLC: non-small cell lung carcinoma; OS: overall survival; PBMC: peripheral blood mononuclear cells; RBP: RNA-binding proteins; RL: Renilla; RLU: relative light units; TAP: transporter associated with antigen processing; tpn: tapasin; UTR: untranslated region.

Dataset Information

MiR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.

Publications

miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11.

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