Integrated Interaction Network of MicroRNA Target Genes in Keloid Scarring

Lyu, Lechun; Zhao, Yu; Lu, Hongquan; Liu, Zijie; Guo, Jinming; Lü, Di; Li, Xiang

doi:10.1007/s40291-018-0378-0

Cited by 13 publications

(10 citation statements)

References 99 publications

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“…Targeting miRNAs could potentially aid the management of keloid scars, as miRNAs play significant roles in keloids. 165,166 The miRNA miRNA-29 negatively regulates fibrosis and miRNA-29 mimics have been proven to prevent pulmonary fibrosis in mouse models. 167 The biggest major open question is: what are the changes to the normal skin epigenetics that result in keloid formation and progression?…”

Section: Targ E Ting Mirna Smentioning

confidence: 99%

The epigenetics of keloids

Stevenson

Deng

Allahham

et al. 2021

Experimental Dermatology

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Keloid scarring is a fibroproliferative disorder of the skin of unknown pathophysiology, characterised by fibrotic tissue that extends beyond the boundaries of the original wound. 1 Keloids develop as a result of disturbance to skin architecture by any wound, and have a strong genetic component, appearing in ethnicities with darker skin pigmentation. 1 There are estimated to be over 11 million keloids in the developed world, with the global number unknown but expected to be higher. 2 Current dogma suggests keloid development follows a similar pathway to normal wound healing but with chronic progression, suggesting disturbance in the fine control of cellular functions that occur during wound healing. 3 Epigenetics, defined as non-base-pair sequence alterations to the DNA, is a key regulator of cell functions, and aberrant epigenetic modifications have been found to contribute to many pathologies, including keloid scars. Our knowledge of progressive fibrosis remains limited, and therapeutic options are few and commonly ineffective, with keloids commonly recurring even after surgery and adjunct treatments. There is an urgent need to gain critical knowledge that will allow us to design better therapeutic strategies and provide evidence to support clinical decisions. This review will explore the current knowledge of the contribution of epigenetic modifications such as DNA methylation, histone modification, microRNAs, long non-coding RNAs to keloid scar formation and progression, and potential treatments utilising modifiers of these processes.

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Section: Targ E Ting Mirna Smentioning

confidence: 99%

The epigenetics of keloids

Stevenson

Deng

Allahham

et al. 2021

Experimental Dermatology

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“…Expression of miRNAs in keloid tissue was shown to be signi cantly different from that of normal tissue. Among the miRNAs involved in keloid pathogenesis, miRNA-21, miRNA-141-3p, miRNA-181a, and miRNA-205 were thought to upregulate broblast proliferation and depress apoptosis of keloid-derived broblasts through the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway [17]. Drugs that indirectly target the biochemical microenvironments of keloids include growth factors (e.g., TGF-bs, bFGF, and VEGF), immunomodulators (e.g., tacrolimus, trehalose, IFN, and imiquimod), and anti-in ammatory drugs (e.g., IL-10 and IL-6) [18][19][20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Líu

Shan

Wang

et al. 2020

Preprint

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Background: Keloids are benign fibroproliferative skin tumors that can cause disfigurement and disability. Although current research has sought to examine keloids from the perspectives of genetics, inflammation, immunity, and tumorigenesis, their pathological mechanisms remain unclear. Methods: In this study, we used three datasets of tumor immune gene expression profiling from the normal skin tissue of keloid patients (N group), inflammation tissue of keloid patients (I group), and keloid tissue of keloid patients (K group) to describe the occurrence and characteristics of keloid development. Tumor immune-related genes were analyzed, and the differentially expressed genes (DEGs) between the three groups were compared. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to determine the main functions of the differentially expressed genes and keloid-related pathways. Results: We identified several genes that may play an important role in keloid development. These genes are CCR1, SELL, CCR7, CD40LG, CD69, CXCL8, ITGAM, ITGAX, CD86, and CXCL9. GO analysis revealed that there were variations in biological processes (BP) between I group and N group, including regulation of lymphocyte activation and T-cell activation. Similar variations were also found between I group and K group, which may play an important role in keloid initiation and formation. Variations in molecular function (MF) were markedly enriched in cytokine receptor binding and receptor ligand activity. Analysis of the KEGG pathway between I group and N group revealed that DEGs were primarily enriched in cytokine−cytokine receptor interaction and viral protein interaction with cytokine and cytokine receptor. We identified a higher proportion of M2 macrophages in N group than in I group, although the difference was not obvious. M1 macrophage production differed significantly between I group and K group. The proportions of CD8+T cells varied significantly between N group and K group. We traced multiple tumor immune-related hub genes from keloid formation and analyzed immune cell subsets in keloid development. Possible molecular mechanisms were described in this study using bioinformatics. Conclusions: These results provide another possibility to elucidate keloid pathogenesis and therapeutic targets in terms of tumor immune gene expression.

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“…Interestingly, miRNAs are characterized by dynamic changes during embryonic development and usually suppress expression of factors in foetal wounds 99 . In Table 2, we present a summary of research primarily focused on the impact of miRNAs in scar formation during the adult stage 100‐120 . Differentially expressed miRNAs have been detected between scar lesions in adult versus embryonic skin 36,121 .…”

Section: Involvement Of Diverse Moleculesmentioning

confidence: 99%

Advances in scarless foetal wound healing and prospects for scar reduction in adults

Yin

Yuan

et al. 2020

Cell Proliferation

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Healing after mammalian skin injury involves the interaction between numerous cellular constituents and regulatory factors, which together form three overlapping phases: an inflammatory response, a proliferation phase and a remodelling phase. Any slight variation in these three stages can substantially alter the healing process and resultant production of scars. Of particular significance are the mechanisms responsible for the scar‐free phenomenon observed in the foetus. Uncovering such mechanisms would offer great expectations in the treatment of scars and therefore represents an important area of investigation. In this review, we provide a comprehensive summary of studies on injury‐induced skin regeneration within the foetus. The information contained in these studies provides an opportunity for new insights into the treatment of clinical scars based on the cellular and molecular processes involved.

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Integrated Interaction Network of MicroRNA Target Genes in Keloid Scarring

Cited by 13 publications

References 99 publications

The epigenetics of keloids

The epigenetics of keloids

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Advances in scarless foetal wound healing and prospects for scar reduction in adults

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