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.

中文翻译：

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LncRNA FPASL 通过 DNMT3b 在增生性瘢痕中的 DNA 甲基化抑制成纤维细胞增殖。

长链非编码 RNA (lncRNA) 越来越多地被认为是细胞增殖、凋亡和分化的关键调节因子。然而，在增生性瘢痕的背景下，特定 lncRNA 的分子机制在很大程度上仍不清楚。在这里，我们发现 lncRNA FPASL（成纤维细胞增殖相关的 LncRNA）在 HS 中下调，并且 FPASL 减少成纤维细胞增殖和集落形成并阻断细胞周期进程。使用 GO 注释富集分析和 AZC（一种特定的 DNA 甲基化抑制剂），我们确定 DNA 甲基化是导致增生性瘢痕中 FPASL 下调的原因。随后的研究表明，DNMT3b 的高表达会抑制 HS 中 FPASL 的表达。机制研究表明，在用 LNA-FPASL 转染后成纤维细胞增殖显着增加，这进一步被 DNMT3b 的敲低所抑制。因此，我们的研究表明 DNMT3b 介导 lncRNA FPASL 启动子的超甲基化，lncRNA FPASL 的下调促进增生性瘢痕中的成纤维细胞增殖。