Dataset Information

Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

ABSTRACT: miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissues. Further experiments revealed that the protein tyrosine phosphatase receptor type M (PTPRM) gene was the host gene of bta-miR-2285o-3p and that two linked SNPs in bta-mir-2285o precursor affected the biogenesis of mature miRNA (bta-miR-2285o-3p). Functional analysis in vitro indicated that bta-miR-2285o-3p attenuated hypoxia-induced apoptosis by targeting very low-density lipoprotein receptor (VLDLR), phosphatase and tensin homolog (PTEN) and caspase-3. Expression level analysis in vivo revealed the high negative Pearson's correlation between bta-miR-2285o-3p and caspase3 in yak, highlighting the potential important roles of bta-miR-2285o-3p in yak high-altitude adaptation. Our study provides a typical model for deciphering the function of miRNAs in environmental adaptation.

SUBMITTER: Zhang J

PROVIDER: S-EPMC9298924 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

Zhang J J Long K K Wang J J Zhang J J Jin L L Tang Q Q Li X X Ma J J Li M M Jiang A A

Animal genetics 20211122 1

miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissue ...[more]

PMID: 34807998

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Project description:Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics. First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p. Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

Dataset Information

Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

Publications

Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

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