Mounting evidence has reported that microRNAs (miRNAs) play irreplaceable roles in the development of keloid fibrosis. miR-4417 has been reported to contribute to nickel chloride-promoted lung epithelial cell fibrogenesis and tumorigenesis. However, whether miR-4417 is involved in keloid fibrogenesis as well as its underlying mechanisms remain largely elusive. In this study, the expression levels of miR-4417 and CyclinD1 in keloid tissues and fibroblasts were examined by qRT-PCR. Cell proliferation was determined by CCK assay. Western blot and flow cytometry were performed to evaluate cell apoptosis. Cell migration and invasion were measured by Transwell assay. Luciferase reporter assay was used to confirm the relationship between miR-4417 and CyclinD1. As a result, we found that miR-4417 was significantly down-regulated in keloid tissues and fibroblasts. miR-4417 up-regulation led to the suppression of proliferation, migration, and invasion, while induced cell apoptosis in keloid fibroblasts. However, miR-4417 depletion exerted an opposite effect. CyclinD1 harbored the binding sites with miR-4417. Besides, the expression of CyclinD1 was evidently decreased in keloid tissues and fibroblasts. Meanwhile, miR-4417 was negatively correlated with CyclinD1 in keloid tissue. The effect of CyclinD1 knockdown on keloid fibroblasts was similar to that of miR-4417 overexpression. Furthermore, the elevated of CyclinD1 expression rescued the effect of miR-4417 up-regulation on keloid fibroblasts. miR-4417/CyclinD1 axis was required for cell proliferation, apoptosis, migration, and invasion in keloid fibroblasts. In conclusion, miR-4417 and CyclinD1 may be potential therapeutic targets for the treatment of keloid.

中文翻译：

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miR-4417 通过抑制 CyclinD1 抑制瘢痕疙瘩纤维化生长

越来越多的证据表明，microRNA (miRNA) 在瘢痕疙瘩纤维化的发展中起着不可替代的作用。据报道，miR-4417 有助于氯化镍促进的肺上皮细胞纤维化和肿瘤发生。然而，miR-4417 是否参与瘢痕疙瘩纤维化及其潜在机制在很大程度上仍然难以捉摸。本研究通过qRT-PCR检测了瘢痕疙瘩组织和成纤维细胞中miR-4417和CyclinD1的表达水平。通过CCK测定确定细胞增殖。进行蛋白质印迹和流式细胞术以评估细胞凋亡。通过Transwell测定测量细胞迁移和侵袭。荧光素酶报告基因检测用于确认 miR-4417 和 CyclinD1 之间的关系。因此，我们发现 miR-4417 在瘢痕疙瘩组织和成纤维细胞中显着下调。miR-4417 上调导致增殖、迁移和侵袭的抑制，同时诱导瘢痕疙瘩成纤维细胞的细胞凋亡。然而，miR-4417 耗竭会产生相反的效果。CyclinD1 具有与 miR-4417 的结合位点。此外，CyclinD1在瘢痕疙瘩组织和成纤维细胞中的表达明显降低。同时，miR-4417与瘢痕疙瘩组织中的CyclinD1呈负相关。CyclinD1 敲低对瘢痕疙瘩成纤维细胞的影响与 miR-4417 过表达的影响相似。此外，CyclinD1 表达的升高挽救了 miR-4417 上调对瘢痕疙瘩成纤维细胞的影响。miR-4417/CyclinD1 轴是瘢痕疙瘩成纤维细胞的细胞增殖、凋亡、迁移和侵袭所必需的。