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微小 RNA-198 通过抑制十号染色体缺失的磷酸酶和张力蛋白同源物表达促进狼疮肾炎进展。

MicroRNA‑198 contributes to lupus nephritis progression by inhibition of phosphatase and tensin homology deleted on chromosome ten expression.

机构信息

Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):7813-7820. doi: 10.3892/mmr.2017.7527. Epub 2017 Sep 19.

DOI:10.3892/mmr.2017.7527
PMID:28944868
Abstract

A number of short noncoding microRNAs (miRs) have been demonstrated to be highly expressed in many kidney diseases such as renal cancer and lupus nephritis (LN); however, these results have not been extensively investigated. The aim of the present study was to investigate the expression and function of miR‑198 in LN based on the previous studies. miR‑198 expression level in systemic lupus erythematosus (SLE) patients was determined to determine its clinicopathological significance and effect on glomerular cell proliferation. It was demonstrated that higher expression of miR‑198 was observed in patients with SLE, and was correlated with disease activity. Bioinformatics prediction and luciferase assays were used to demonstrate that miR‑198 could directly bind to the phosphatase and tensin homology deleted on chromosome ten (PTEN) 3'‑untranslated region. Furthermore, miR‑198 overexpression reduced PTEN expression levels, while miR‑198 silencing increased its expression at both the mRNA and protein level. Furthermore, there was a negative association between miR‑198 and PTEN in the patients with active SLE. Thus, miR‑198 may promote proliferation and contribute to SLE progression by targeting PTEN.

摘要

许多短的非编码 microRNAs(miRs)在许多肾脏疾病中如肾肿瘤和狼疮肾炎(LN)中被证实高度表达;然而,这些结果尚未被广泛研究。本研究旨在基于先前的研究,调查 miR-198 在 LN 中的表达和功能。通过测定系统性红斑狼疮(SLE)患者中 miR-198 的表达水平,以确定其临床病理意义及其对肾小球细胞增殖的影响。结果表明,SLE 患者中 miR-198 的表达水平较高,且与疾病活动度相关。生物信息学预测和荧光素酶报告基因检测实验表明,miR-198 可直接与第 10 号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)3'UTR 结合。此外,miR-198 过表达降低了 PTEN 的表达水平,而 miR-198 沉默则增加了其在 mRNA 和蛋白水平的表达。此外,在活动期 SLE 患者中,miR-198 与 PTEN 之间呈负相关。因此,miR-198 可能通过靶向 PTEN 促进增殖并促进 SLE 的进展。

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