miR-194-5p serves a suppressive role in human keloid fibroblasts via targeting NR2F2

miR-194-5p 通过靶向 NR2F2 在人类瘢痕疙瘩成纤维细胞中发挥抑制作用

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作者:Qijun Xu, Shengjun Jiang

Abstract

Keloids are a skin fibrotic disease that cause a number of problems for reconstructive surgeons. MicroRNAs (miRs) are crucial for the development of keloids. The present study aimed to investigate the function of the miR‑194‑5p/nuclear receptor subfamily 2 group F member 2 (NR2F2) interactome in human keloid fibroblasts. Microarray analysis was performed to identify key genes that may participate in keloid progression. The expression levels of miR‑194‑5p and NR2F2 mRNA in normal human skin fibroblasts (HSFs) and human keloid fibroblasts (KEL‑FIBs) were measured via reverse transcription‑quantitative PCR. Furthermore, cell proliferation, apoptosis, migration and invasion were assessed in KEL‑FIB cells. Following NR2F2 knockdown and miR‑194‑5p inhibition, NR2F2 expression was measured via western blotting. The microarray analysis identified NR2F2 as a key gene related to keloids. The regulatory association between miR‑194‑5p and NR2F2 was identified using TargetScan Human (version 7.2) and verified by performing a dual‑luciferase reporter assay. miR‑194‑5p expression was decreased in KEL‑FIB cells compared with HSF cells, and miR‑194‑5p overexpression inhibited the aggressive phenotypes of KEL‑FIB cells compared with the negative control group. Meanwhile, NR2F2 expression was negatively correlated with miR‑194‑5p expression. NR2F2 knockdown and miR‑194‑5p overexpression displayed similar effects on KEL‑FIB cells. Moreover, NR2F2 knockdown effectively reversed miR‑194‑5p inhibitor‑mediated effects in keloid fibroblasts. The present study indicated that the novel miR/194‑5p/NR2F2 interactome might be involved in the progression of keloid aggression and may serve as a potential therapeutic target for human keloid in the future.

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