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环状 RNA hsa_circ_0043688 作为 microRNA-145-5p 的竞争性内源性 RNA 通过成纤维细胞生长因子-2 促进瘢痕疙瘩的进展。

Circular RNA hsa_circ_0043688 serves as a competing endogenous RNA for microRNA-145-5p to promote the progression of Keloids via Fibroblast growth factor-2.

机构信息

Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

J Clin Lab Anal. 2022 Aug;36(8):e24528. doi: 10.1002/jcla.24528. Epub 2022 Jun 26.

Abstract

BACKGROUND

Keloids are benign fibroproliferative skin tumors. Circular RNA (circRNA) hsa_circ_0043688 has been exhibited to the freakishly expressed in keloid tissues. Here, we aimed to investigate the regulatory network of hsa_circ_0043688 in the pathological process of keloid.

METHODS

Hsa_circ_0043688, microRNA-145-5p (miR-145-5p), and Fibroblast growth factor-2 (FGF2) level were detected using RT-qPCR. Cell viability, proliferation, apoptosis, invasion, and migration were investigated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays, respectively. Western blot analysis of protein levels of FGF2, CyclinD1, Collagen I, and Collagen III. After the prediction of Circinteractome and Starbase, their interaction was verified based on a dual-luciferase reporter and RIP assays.

RESULTS

Increased hsa_circ_0043688 and FGF2, and decreased miR-145-5p in keloids samples and fibroblasts were found. Also, hsa_circ_0043688 absence hindered proliferation, invasion, migration, and boost apoptosis of keloid fibroblasts. In mechanism, hsa_circ_0043688 modulated FGF2 content via sponging miR-145-5p.

CONCLUSION

Hsa_circ_0043688 knockdown inhibited cell growth and metastasis of keloid fibroblasts via miR-145-5p/FGF2, providing a new mechanism to understand the keloid progression.

摘要

背景

瘢痕疙瘩是良性的纤维增生性皮肤肿瘤。环状 RNA(circRNA)hsa_circ_0043688 在瘢痕疙瘩组织中表现出异常表达。在这里,我们旨在研究 hsa_circ_0043688 在瘢痕疙瘩病理过程中的调控网络。

方法

使用 RT-qPCR 检测 hsa_circ_0043688、microRNA-145-5p(miR-145-5p)和 Fibroblast growth factor-2(FGF2)的水平。使用 Cell Counting Kit-8(CCK-8)、5-ethynyl-2'-deoxyuridine(EdU)、流式细胞术、Transwell 和划痕愈合实验分别研究细胞活力、增殖、凋亡、侵袭和迁移。Western blot 分析 FGF2、CyclinD1、Collagen I 和 Collagen III 的蛋白水平。在 Circinteractome 和 Starbase 的预测之后,基于双荧光素酶报告和 RIP 实验验证它们的相互作用。

结果

在瘢痕疙瘩样本和成纤维细胞中发现 hsa_circ_0043688 和 FGF2 增加,miR-145-5p 减少。此外,hsa_circ_0043688 的缺失抑制了瘢痕疙瘩成纤维细胞的增殖、侵袭、迁移和促进凋亡。在机制上,hsa_circ_0043688 通过海绵吸附 miR-145-5p 调节 FGF2 含量。

结论

hsa_circ_0043688 敲低通过 miR-145-5p/FGF2 抑制瘢痕疙瘩成纤维细胞的生长和转移,为理解瘢痕疙瘩进展提供了新的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8913/9396203/9d65c357f09f/JCLA-36-e24528-g009.jpg

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