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小 RNA 深度测序揭示 IgA 肾病患者外周血单个核细胞中的新 miRNA。

Small RNA deep sequencing reveals novel miRNAs in peripheral blood mononuclear cells from patients with IgA nephropathy.

机构信息

Blood Purification Center, Air Force Hospital of Southern Theater, PLA, Guangzhou, Guangdong 510062, P.R. China.

The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.

出版信息

Mol Med Rep. 2020 Oct;22(4):3378-3386. doi: 10.3892/mmr.2020.11405. Epub 2020 Aug 3.

DOI:10.3892/mmr.2020.11405
PMID:32945407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7453501/
Abstract

Peripheral blood mononuclear cells (PBMCs) contribute to the deposition of immunoglobulin A (IgA) and progression of IgA nephropathy (IgAN). This study was performed to identify novel microRNAs (miRNAs/miRs) associated with IgAN. Small RNAs were isolated from PBMCs collected from 10 healthy participants and 10 patients with IgAN; the RNAs were then subjected to high‑throughput small RNA sequencing. The results showed that miRNAs constituted 70.33 and 69.83% of small RNAs in PBMCs from healthy participants and patients with IgAN, respectively. In total, 44 differentially expressed miRNAs were identified, of which 34 were upregulated and 10 were downregulated. Among these differentially expressed miRNAs, most showed novel associations with IgAN, except miR‑148a‑3p, miR‑184 and miR‑200a. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes of the differentially expressed miRNAs were primarily enriched in cancer pathways, the PI3K‑Akt signaling pathway and MAPK pathways, all of which control cell proliferation and gene expression. Moreover, miR‑3121‑3p, miR‑203a‑3p and miR‑200a‑3p may regulate core 1 synthase, glycoprotein‑N‑acetylgalactosamine 3‑β‑galactosyltransferase 1 (C1GALT1) expression by binding to its 3' untranslated region. In conclusion, 44 differentially expressed miRNAs were discovered, 41 of which were newly found to be associated with IgAN. The differentially expressed miRNAs may regulate the progression of IgAN by controlling the behavior of PBMCs or deposition of IgA via targeting of signaling pathways or expression of C1GALT1. These findings may provide a basis for further research regarding IgAN diagnosis and therapy.

摘要

外周血单个核细胞(PBMCs)有助于免疫球蛋白 A(IgA)的沉积和 IgA 肾病(IgAN)的进展。本研究旨在鉴定与 IgAN 相关的新型 microRNAs(miRNAs/miRs)。从小鼠 PBMCs 中分离出 10 名健康参与者和 10 名 IgAN 患者的小分子 RNA;然后对这些 RNA 进行高通量小分子 RNA 测序。结果表明,miRNAs 分别占健康参与者和 IgAN 患者 PBMCs 中小分子 RNA 的 70.33%和 69.83%。总共鉴定出 44 个差异表达的 miRNAs,其中 34 个上调,10 个下调。在这些差异表达的 miRNAs 中,大多数与 IgAN 具有新的关联,除了 miR-148a-3p、miR-184 和 miR-200a。此外,京都基因与基因组百科全书通路分析显示,差异表达 miRNA 的靶基因主要富集在癌症通路、PI3K-Akt 信号通路和 MAPK 通路中,这些通路均控制细胞增殖和基因表达。此外,miR-3121-3p、miR-203a-3p 和 miR-200a-3p 可能通过与核心 1 合酶的 3'非翻译区结合来调节核心 1 合酶、糖蛋白-N-乙酰半乳糖胺 3-β-半乳糖基转移酶 1(C1GALT1)的表达。总之,发现了 44 个差异表达的 miRNAs,其中 41 个与 IgAN 新发现相关。差异表达的 miRNAs 可能通过调控信号通路或 C1GALT1 的表达来调节 IgAN 的进展,从而控制 PBMCs 的行为或 IgA 的沉积。这些发现可能为 IgAN 的诊断和治疗提供进一步研究的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/318f/7453501/17068ba1eb66/MMR-22-04-3378-g06.jpg
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