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Abstract：
BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids.
METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions.
RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-β, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway.
CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.
METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions.
RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-β, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway.
CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.
摘要：
背景：我们的研究旨在描述在肥厚性瘢痕（HS）和瘢痕疙瘩的情况下miRSNP-microRNA-基因通路的相互作用。
方法：我们进行了一项涉及差异表达分析的计算生物学研究，以鉴定HS和瘢痕疙瘩组织中与正常皮肤相比的基因及其mRNA，确定关键的枢纽基因并丰富其功能作用，通过生物信息学全面分析microRNA靶基因和相关信号通路，识别MiRSNP，并构建基于通路的网络来说明miRSNP-miRNA-基因-信号通路的相互作用。
结果：我们的结果揭示了总共429个hub基因，与癌症中蛋白聚糖相关的信号通路有很强的富集，病灶粘连,TGF-β,PI3K/Akt,和EGFR酪氨酸激酶抑制剂耐药。特别值得注意的是粘着斑和PI3K/Akt信号通路之间的大量串扰，使它们更容易受到microRNA的调节。我们还鉴定了特定的miRNA，包括miRNA-1279、miRNA-429和miRNA-302e，有多个SNP位点,与miRSNPsrs188493331和rs78979933施加对显著数量的miRNA靶基因的控制。此外，我们观察到miRSNPrs188493331与microRNA302e共享一个位置，microRNA202a-3p,和microRNA20b-5p，这三种microRNA共同靶向基因LAMA3，它是粘着斑信号通路的组成部分。
结论：该研究成功揭示了miRSNP之间的复杂相互作用，miRNA,基因，和信号通路，阐明导致HS和瘢痕疙瘩形成的遗传因素。
方法：我们进行了一项涉及差异表达分析的计算生物学研究，以鉴定HS和瘢痕疙瘩组织中与正常皮肤相比的基因及其mRNA，确定关键的枢纽基因并丰富其功能作用，通过生物信息学全面分析microRNA靶基因和相关信号通路，识别MiRSNP，并构建基于通路的网络来说明miRSNP-miRNA-基因-信号通路的相互作用。
结果：我们的结果揭示了总共429个hub基因，与癌症中蛋白聚糖相关的信号通路有很强的富集，病灶粘连,TGF-β,PI3K/Akt,和EGFR酪氨酸激酶抑制剂耐药。特别值得注意的是粘着斑和PI3K/Akt信号通路之间的大量串扰，使它们更容易受到microRNA的调节。我们还鉴定了特定的miRNA，包括miRNA-1279、miRNA-429和miRNA-302e，有多个SNP位点,与miRSNPsrs188493331和rs78979933施加对显著数量的miRNA靶基因的控制。此外，我们观察到miRSNPrs188493331与microRNA302e共享一个位置，microRNA202a-3p,和microRNA20b-5p，这三种microRNA共同靶向基因LAMA3，它是粘着斑信号通路的组成部分。
结论：该研究成功揭示了miRSNP之间的复杂相互作用，miRNA,基因，和信号通路，阐明导致HS和瘢痕疙瘩形成的遗传因素。
