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长链非编码RNA MEG3-微小RNA-21及内质网应激蛋白在寻常型银屑病发病机制中的可能作用

Possible Role of lncRNA MEG3-microRNA-21 and Endoplasmic Reticulum (ER) Stress Proteins in the Pathogenesis of Psoriasis Vulgaris.

作者信息

Ahmed Nour Zeinab, Elwan Yasmine, Nassar Yasser, Fathy Elmasry Maha, Rashed Laila, Salama Ashour Sara

机构信息

Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Maha Fathy Elmasry, Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Rep Biochem Mol Biol. 2022 Oct;11(3):367-376. doi: 10.52547/rbmb.11.3.367.

Abstract

BACKGROUND

Psoriasis is a chronic inflammatory immune mediated disease arising from interaction between genetic risk variants and the environment. Maternally expressed gene3 (MEG3) is a long noncoding RNA (lncRNA) known for gene transcription regulation and inhibiting proliferation. MEG3 competes with microRNA (miRNA-21) influencing cell proliferation and apoptosis balance. Endoplasmic reticulum (ER) stress proteins promote cell survival via unfolded protein response (UPR) influenced by MEG3. We aimed to detect the possible role of MEG3, miRNA-21 and ER stress proteins in pathogenesis of psoriasis vulgaris.

METHODS

Human GRP78, ATF6, caspase3 tissue levels were assayed by Enzyme Linked Immunosorbent Assay (ELISA). Assessment of long non-coding MEG3 and miRNA 21 expressions was done by quantitative real time polymerase chain reaction (qRT-PCR).

RESULTS

Expression of MEG3 was significantly downregulated, while miRNA-21 was remarkably upregulated, ER stress proteins GRP78, ATF6, and caspase 3 all showed low levels in homogenized psoriatic lesions when compared to normal skin. miRNA 21 and MEG3 were identified as possible diagnostic markers for psoriasis vulgaris.

DISCUSSION

MEG3 is barely expressed in psoriatic lesions while miRNA-21 expression is remarkably elevated but when correlated to each other there was unexpected positive correlation. MEG3 and miRNA-21 were identified as possible diagnostic markers for psoriasis. Undifferentiated psoriatic lesions have very weak UPR.

摘要

背景

银屑病是一种由遗传风险变异与环境相互作用引起的慢性炎症性免疫介导疾病。母系表达基因3(MEG3)是一种长链非编码RNA(lncRNA),以基因转录调控和抑制增殖而闻名。MEG3与微小RNA(miRNA-21)竞争,影响细胞增殖和凋亡平衡。内质网(ER)应激蛋白通过受MEG3影响的未折叠蛋白反应(UPR)促进细胞存活。我们旨在检测MEG3、miRNA-21和ER应激蛋白在寻常型银屑病发病机制中的可能作用。

方法

采用酶联免疫吸附测定(ELISA)检测人GRP78、ATF6、caspase3组织水平。通过定量实时聚合酶链反应(qRT-PCR)评估长链非编码MEG3和miRNA 21的表达。

结果

与正常皮肤相比,银屑病皮损匀浆中MEG3表达显著下调,而miRNA-21显著上调,ER应激蛋白GRP78、ATF6和caspase 3均呈低水平。miRNA 21和MEG3被确定为寻常型银屑病的可能诊断标志物。

讨论

MEG3在银屑病皮损中几乎不表达,而miRNA-21表达显著升高,但两者相互关联时存在意外的正相关。MEG3和miRNA-21被确定为银屑病的可能诊断标志物。未分化的银屑病皮损具有非常微弱的UPR。

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Psoriasis: a brief overview.银屑病:简要概述。
Clin Med (Lond). 2021 May;21(3):170-173. doi: 10.7861/clinmed.2021-0257.
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Dysregulated epigenetic modifications in psoriasis.银屑病中失调的表观遗传修饰。
Exp Dermatol. 2021 Aug;30(8):1156-1166. doi: 10.1111/exd.14332. Epub 2021 Apr 5.
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The eminent roles of ncRNAs in the pathogenesis of psoriasis.非编码RNA在银屑病发病机制中的重要作用。
Noncoding RNA Res. 2020 Jul 3;5(3):99-108. doi: 10.1016/j.ncrna.2020.06.002. eCollection 2020 Sep.

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