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miR-762 的上调抑制了系统性红斑狼疮和神经精神性系统性红斑狼疮中 GIPC3 的表达。

Upregulation of microRNA-762 suppresses the expression of GIPC3 in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus.

机构信息

Department of Rheumatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, P.R.China.

Department of Nursing, Xingtai Medical College, Xingtai, Hebei, P.R.China.

出版信息

Immun Inflamm Dis. 2022 Nov;10(11):e719. doi: 10.1002/iid3.719.

DOI:10.1002/iid3.719
PMID:36301034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9552983/
Abstract

BACKGROUND

Systemic lupus erythematosus (SLE), especially neuropsychiatric SLE (NPSLE), is a complex systemic autoimmune disease, characterized by variable course and multiple organ dysfunction. Our study aimed to identify crucial microRNA (miRNAs) in SLE and NPSLE.

METHODS

Totally 12 cases of serum specimens were collected from General Hospital of Ningxia Medical University (SLE = 4, NPSLE = 4, control = 4). After miRNA sequencing, differential expression analysis, miRNA target prediction, and miRNA-messenger RNA (mRNA) regulatory network construction were performed to identify the hub miRNAs. The expression of target gene was determined by quantitative reverse transcription-polymerase chain reaction and Western blot.

RESULTS

There were 79 and 59 differentially expressed miRNAs (DEmiRNAs) in NPSLE versus Control, and SLE versus Control, respectively. Among 35 overlapped DEmiRNAs, 5 upregulated miRNAs' (hsa-miR-762, hsa-miR-4270, hsa-miR-3663-3p, hsa-miR-4778-5p, and hsa-miR-4516) target genes were supported by at least six databases. The miRNA-mRNA network indicated that core miRNA hsa-miR-762 regulated 1270 target genes. MiR-762 was significantly upregulated in SLE and NPSLE, and over expression of miR-762 significantly suppressed GIPC PDZ domain containing family member 3 (GIPC3) expression in SLE and NPSLE.

CONCLUSIONS

Upregulation of hub miRNA miR-762 can suppress the expression of GIPC3 in both SLE and NPSLE samples, which is probably involved in the development of SLE and NPSLE. Meanwhile, along with the development from SLE to NPSLE, miR-762 exhibits higher expression.

摘要

背景

系统性红斑狼疮(SLE),尤其是神经精神性狼疮(NPSLE),是一种复杂的系统性自身免疫性疾病,其特征为病程多变且多器官功能障碍。本研究旨在鉴定 SLE 和 NPSLE 中的关键 microRNA(miRNA)。

方法

我们从宁夏医科大学总医院收集了 12 例血清标本(SLE = 4,NPSLE = 4,对照组 = 4)。进行 miRNA 测序后,进行差异表达分析、miRNA 靶标预测以及 miRNA-messenger RNA(mRNA)调控网络构建,以鉴定关键 miRNA。通过定量逆转录-聚合酶链反应(qRT-PCR)和 Western blot 检测靶基因的表达。

结果

NPSLE 与对照组、SLE 与对照组分别有 79 个和 59 个差异表达 miRNA(DEmiRNA)。在 35 个重叠的 DEmiRNA 中,有 5 个上调 miRNA(hsa-miR-762、hsa-miR-4270、hsa-miR-3663-3p、hsa-miR-4778-5p 和 hsa-miR-4516)的靶基因得到了至少 6 个数据库的支持。miRNA-mRNA 网络表明核心 miRNA hsa-miR-762 调控了 1270 个靶基因。miR-762 在 SLE 和 NPSLE 中均显著上调,且在 SLE 和 NPSLE 中过表达 miR-762 可显著抑制 GIPC PDZ 结构域家族成员 3(GIPC3)的表达。

结论

关键 miRNA miR-762 的上调可抑制 SLE 和 NPSLE 样本中 GIPC3 的表达,这可能与 SLE 和 NPSLE 的发生发展有关。同时,随着 SLE 向 NPSLE 的发展,miR-762 表现出更高的表达水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/89d91c238d5a/IID3-10-e719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/361c633018cd/IID3-10-e719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/256ea28626bd/IID3-10-e719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/58211da66fcd/IID3-10-e719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/89d91c238d5a/IID3-10-e719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/361c633018cd/IID3-10-e719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/256ea28626bd/IID3-10-e719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/58211da66fcd/IID3-10-e719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c152/9552983/89d91c238d5a/IID3-10-e719-g002.jpg

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