CircPDE7B/miR-661 axis accelerates the progression of human keloid fibroblasts by upregulating fibroblast growth factor 2 (FGF2).

Abstract

Circular RNAs (circRNAs) are implicated in keloidogenesis and development. We aimed to investigate the role of a new identified phosphodiesterase 7B-derived circRNA (hsa_circ_0002198; henceforth named as PDE7B) in human keloid fibroblasts (HKFs) and to further confirm its mechanism via competing endogenous RNA (ceRNA) network. Transcriptional and translational levels of circPDE7B, microRNA (miR)-661, fibroblast growth factor 2 (FGF2), cleaved caspase3, B-cell lymphoma (bcl)-2, and bcl-2-associated X protein (bax) were detected by real-time quantitative PCR and western blotting. Relationship among circPDE7B, miR-661, and FGF2 was confirmed by bioinformatics algorithm, dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and Spearman's rank correlation analysis. Cell progression was measured by cell counting kit-8 assay, 5-ethynyl-2-deoxyuridine assay, transwell assays, and flow cytometry. Expression of circPDE7B was upregulated in human keloid tissues and HKFs, accompanied with miR-661 downregulation and FGF2 upregulation. High circPDE7B accelerated proliferation, migration, and invasion, and inhibited apoptosis. These effects were paralleled with increased bcl-2 and decreased cleaved caspase3 and bax. Moreover, low circPDE7B played opposite effects to high circPDE7B. Restoring miR-661 could suppress HKFs progression, while blocking miR-661 could facilitate that. Notably, miR-661 was directly sponged by circPDE7B and then directly governed FGF2 gene expression. Deleting miR-661 and re-expressing FGF2 both abrogated the suppression of circPDE7B knockdown in HKFs progression. In conclusion, circPDE7B might contribute to HKFs progression via functioning as ceRNA for miR-661, suggesting a novel circPDE7B/miR-661/FGF2 pathway underlying keloid formation and treatment.

• Authors: Fenglian Wu, Hongbin He, Yanxin Chen, Donglai Zhu, Tao Jiang, Jiaxin Wang
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 477 Issue 4 Pg. 1113-1126 (Apr 2022) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 35079927 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• MIRN661 microRNA, human
• MicroRNAs
• RNA, Circular
• Fibroblast Growth Factor 2

Topics

• Cell Line
• Fibroblast Growth Factor 2 (biosynthesis, genetics)
• Fibroblasts (metabolism)
• Humans
• Keloid (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• RNA, Circular (genetics, metabolism)
• Signal Transduction
• Up-Regulation