生物
表达数量性状基因座
发病机制
基因表达
外周血单个核细胞
单核苷酸多态性
免疫学
分子生物学
基因
癌症研究
遗传学
体外
基因型
作者
Pei He,Fei‐Yan Deng,Binghua Wang,Long‐Fei Wu,X. Y. Zhou,Shu‐Feng Lei
出处
期刊:Gene
[Elsevier]
日期:2022-02-01
卷期号:810: 146059-146059
被引量:2
标识
DOI:10.1016/j.gene.2021.146059
摘要
To identify RA-associated genes and to ascertain epigenetic factors and functional mechanisms underlying RA pathogenesis.Peripheral blood mononuclear cells (PBMC) transcriptome- and proteome- wide gene expressions were profiled in a case-control study sample. Differentially expressed genes (DEGs) were discovered and validated independently. In-house PBMC genome-wide SNP genotyping data, miRNA expression data and DNA methylation data in the same sample were utilized to identify SNPs [expression quantitative trait locus (eQTLs) and protein quantitative trait locus (pQTLs)], miRNAs, and DNA methylation positions (DMPs) regulating key DEG of interest. Lentivirus transfection was conducted to study the effects of RPN2 on T lymphocyte activation, proliferation, apoptosis, and inflammatory cytokine expression. Rpn2 protein level in plasma was quantitated by ELISA to assess its performance in discriminating RA cases and controls.Twenty-two DEGs were discovered in PBMCs. The most significant DEG, i.e., RPN2, was validated to be up-regulated with RA in PBMCs. A complex regulatory network for RPN2 gene expression in PBMCs was constructed, which consists of 38 eQTL and 53 pQTL SNPs, 3 miRNAs and 2 DMPs. Besides, RPN2 expression was significantly up-regulated with RA in primary T lymphocytes, as well as in PHA-activated T lymphocytes. RPN2 over-expression in T lymphocytes significantly inhibited apoptosis and IL-4 expression and promoted proliferation and activation. PBMCs-expressed RPN2 mRNA and plasma Rpn2 protein demonstrated superior and modest performances in discriminating RA cases and controls, respectively.RPN2 gene influences T lymphocyte growth and activation and is involved in the pathogenesis of RA. Rpn2 may serve as a novel protein biomarker for RA diagnosis.
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