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环状 RNA hsa_circ_0057452 通过靶向 microRNA-1225-3p/AF4/FMR2 家族成员 4 轴促进瘢痕疙瘩进展。

Circular RNA hsa_circ_0057452 facilitates keloid progression by targeting the microRNA-1225-3p/AF4/FMR2 family member 4 axis.

机构信息

Wound Repair & Rehabilitation Centre, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei, China.

Department of Dermatology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei, China.

出版信息

Bioengineered. 2022 May;13(5):13815-13828. doi: 10.1080/21655979.2022.2084460.

Abstract

The circular RNA, hsa_circ_0057452, is highly expressed in keloids, but its specific mechanism of action remains unknown. The levels of hsa_circ_0057452, microRNA (miR)-1225-3p, and AF4/FMR2 family member 4 (AFF4) in keloid tissues and keloid fibroblasts (KFs) were determined using quantitative reverse transcription-polymerase chain reaction. Changes in KFs viability, proliferation, apoptosis, and migration were investigated using the cell counting kit-8, bromodeoxyuridine, flow cytometry, and Transwell assays. Luciferase, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the binding relationship among hsa_circ_0057452, miR-1225-3p, and AFF4. We found that hsa_circ_0057452 and AFF4 expression levels were upregulated, whereas miR-1225-3p expression levels were downregulated in keloids. Knockdown of hsa_circ_0057452 or AFF4 suppressed the viability, proliferation, and migration of KFs and induced apoptosis, whereas hsa_circ_0057452 overexpression and miR-1225-3p knockdown showed the opposite trend. Furthermore, hsa_circ_0057452 affected the biological behavior of KFs by releasing AFF4 via sponging of miR-1225-3p. Therefore, our results show that hsa_circ_0057452 promotes keloid progression by targeting miR-1225-3p and regulating AFF4 levels.

摘要

环状 RNA hsa_circ_0057452 在瘢痕疙瘩中高度表达,但具体作用机制尚不清楚。采用实时定量聚合酶链反应检测瘢痕疙瘩组织和瘢痕疙瘩成纤维细胞(KFs)中 hsa_circ_0057452、微小 RNA(miR)-1225-3p 和 AF4/FMR2 家族成员 4(AFF4)的水平。采用细胞计数试剂盒-8、溴脱氧尿苷、流式细胞术和 Transwell 检测法研究 KFs 活力、增殖、凋亡和迁移的变化。通过荧光素酶、RNA 免疫沉淀和 RNA 下拉实验鉴定 hsa_circ_0057452、miR-1225-3p 和 AFF4 之间的结合关系。我们发现 hsa_circ_0057452 和 AFF4 的表达水平上调,而 miR-1225-3p 的表达水平下调在瘢痕疙瘩中。hsa_circ_0057452 或 AFF4 的敲低抑制 KFs 的活力、增殖和迁移并诱导凋亡,而 hsa_circ_0057452 的过表达和 miR-1225-3p 的敲低则表现出相反的趋势。此外,hsa_circ_0057452 通过释放 miR-1225-3p 海绵吸附 AFF4 影响 KFs 的生物学行为。因此,我们的研究结果表明 hsa_circ_0057452 通过靶向 miR-1225-3p 调节 AFF4 水平促进瘢痕疙瘩的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e626/9275943/a202edf286bc/KBIE_A_2084460_UF0001_OC.jpg

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