Keloid scarring is a dermal fibroproliferative response characterized by excessive and progressive deposition of collagen; aetiology and molecular pathology underlying keloid formation and progression remain unclear. Genetic predisposition is important in the pathogenic processes of keloid formation, however, environmental factors and epigenetic mechanisms may also play pivotal roles. Epigenetic modification is a recent area of investigation in understanding the molecular pathogenesis of keloid scarring and there is increasing evidence that epigenetic changes may play a role in induction and persistent activation of fibroblasts in keloid scars. Here we have reviewed three epigenetic mechanisms: DNA methylation, histone modification and the role of non-coding RNAs. We also review the evidence that these mechanisms may play a role in keloid formation - in future, it may be possible that epigenetic markers may be used instead of prognostic or diagnostic markers here. However, there is a significant amount of work required to increase our current understanding of the role of epigenetic modification in keloid disease.

Fibrosis is a common pathological state characterized by the excessive accumulation of extracellular matrix components, but the pathogenesis of the disease is still not clear. Previous studies have shown that microRNA-29 (miR-29) can play pivotal roles in the regulation of a variety of organ fibrosis, including cardiac fibrosis, hepatic fibrosis, lung fibrosis, systemic sclerosis, and keloid. In this review, we outline the structure, expression, and regulation of miR-29 as well as its role in fibrotic diseases.

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Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well‐known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non‐drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/β‐catenin signaling pathway in HCC cells. We further demonstrated that β‐catenin siRNA or salinomycin (an inhibitor of Wnt/β‐catenin pathway) partially rescued ethanol‐induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.

microRNAs (miRNAs) play a pivotal role in the regulation of cell proliferation and apoptosis in keloid scarring. Integrative analysis of the previous miRNA microarray revealed miRNA-31 was among the most frequently altered miRNAs in keloid and hypertrophic scar. Using qRT-PCR, we further validated miRNA-31 was increased in keloid tissues and keloid-derived fibroblasts. Moreover, downregulation of miRNA-31 inhibited the cell proliferation, induced the cell apoptosis and disturbed the cell cycle progression by targeting HIF1AN, a negative modulator of hypoxia inducible factor 1. Through the luciferase reporter assay, HIF1AN was confirmed to be a target of miRNA-31. Further studies demonstrated that miRNA-31 regulated proliferation, apoptosis and cell cycle of keloid-derived fibroblasts by mediating HIF1AN/VEGF signaling pathway. Overall, our findings shed new light on miRNA-31 as a promising therapeutic target in keloid scarring.