长链非编码 RNA MIAT 通过 miR-411-5p/JAG1 轴促进瘢痕疙瘩形成。

IncRNA MIAT Accelerates Keloid Formation by miR-411-5p/JAG1 Axis.

机构信息

Department of Dermatology, University of Electronic Science and Technology of China Hospital, Chengdu 611731, Sichuan, China.

Department of Dermatology, Kun Ming Li Du Medical Beauty Hospital, Kunming 650000, Yunnan, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2023;33(2):81-92. doi: 10.1615/CritRevEukaryotGeneExpr.2022044734.

DOI:10.1615/CritRevEukaryotGeneExpr.2022044734

PMID:36734859

Abstract

The long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) regulates the biological functions of many kinds of cells. The aim of this study is to explore the mechanism of MIAT and how it affects keloid progression. The expressions of MIAT, JAG1, and miR-411-5p in keloid tissues and keloid fibroblasts (KEL FIBs) were quantified by conducting Western blot and quantitative reverse transcription polymerase chain reaction analyses. The influences of MIAT, JAG1, and miR-411-5p on the abilities of KEL FIBs to proliferate, migrate, and invade were assessed by means of the CCK-8, wound healing, and Transwell experiments. To determine the binding relationship among MIAT, JAG1, and miR-411-5p, we performed luciferase reporter and RIP experiments. In keloid tissues and KEL FIBs, MIAT and JAG1 were upregulated while miR-411-5p was downregulated. Knocking-down MIAT or JAG1 significantly inhibited proliferation, migration and invasion. On the contrary, suppressing miR-411-5p expression produced an opposite effect. With regard to mechanisms, MIAT sponged miR-411-5p, which targeted JAG1. MIAT accelerates keloid formation by modulating the miR-411-5p/JAG1 axis.

摘要

长链非编码 RNA（lncRNA）心肌梗塞相关转录物（MIAT）调节多种细胞的生物学功能。本研究旨在探讨 MIAT 的作用机制及其对瘢痕疙瘩进展的影响。通过 Western blot 和定量逆转录聚合酶链反应分析，定量检测瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞（KEL FIB）中 MIAT、JAG1 和 miR-411-5p 的表达。通过 CCK-8、划痕愈合和 Transwell 实验评估 MIAT、JAG1 和 miR-411-5p 对 KEL FIB 增殖、迁移和侵袭能力的影响。通过荧光素酶报告和 RIP 实验确定 MIAT、JAG1 和 miR-411-5p 之间的结合关系。在瘢痕疙瘩组织和 KEL FIB 中，MIAT 和 JAG1 上调，而 miR-411-5p 下调。敲低 MIAT 或 JAG1 显著抑制增殖、迁移和侵袭。相反，抑制 miR-411-5p 的表达则产生相反的效果。就机制而言，MIAT 吸附 miR-411-5p，后者靶向 JAG1。MIAT 通过调节 miR-411-5p/JAG1 轴加速瘢痕疙瘩形成。