LncRNA FPASL suppresses fibroblast proliferation through its DNA methylation via DNMT3b in hypertrophic scar

Autor: Wu Kai, Ma Fang, Shen Jiangyong, Zhang Hui, Wan Yu, He Xi, Yang Anning, Xiong Jiantuan, Jiao Yun, Bai Zhigang, Ma Shengchao, Jiang Yideng, Zhang Huiping, Hao Yinju
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Acta Biochimica et Biophysica Sinica, Vol 54, Pp 1854-1862 (2022)
Druh dokumentu: article
ISSN: 1672-9145
DOI: 10.3724/abbs.2022181
Popis: Long noncoding RNAs (lncRNAs) are increasingly being implicated as key regulators of cell proliferation, apoptosis, and differentiation. However, the molecular mechanisms of specific lncRNAs in the context of hypertrophic scar remain largely unclear. Here, we find that the lncRNA FPASL (fibroblast proliferation-associated LncRNA) is downregulated in HS, and FPASL reduces fibroblast proliferation and colony formation and blocks cell cycle progression. Using GO annotation enrichment analysis along with AZC (a specific inhibitor of DNA methylation), we identify that DNA methylation is responsible for downregulating FPASL in hypertrophic scar. Subsequent studies demonstrate that high expression of DNMT3b inhibits FPASL expression in HS. Mechanistic study reveals a significant increase in fibroblast proliferation after transfection with LNA-FPASL, which is further inhibited by knockdown of DNMT3b. Thus, our study reveals that DNMT3b mediates hypermethylation of the lncRNA FPASL promoter and the downregulation of lncRNA FPASL promotes fibroblast proliferation in hypertrophic scar.
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