Critical genes in human photoaged skin identified using weighted gene co-expression network analysis
Critical genes in human photoaged skin identified using weighted gene co-expression network analysis
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DOI：
10.1016/j.ygeno.2023.110682
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发表时间：
2023-07-25
期刊：
影响因子：
4.4
通讯作者：
Cao，Wenting
中科院分区：
文献类型：
--
作者：
Zhao，Jie;Zhang，Xun;Cao，Wenting
光老化是皮肤特有的，并伴随着肿瘤风险的增加。为了探索皮肤光老化的转录组调控机制，我们手术切除了16个健康供体（8个暴露和8个未暴露）的表皮和真皮层，并使用总RNA-Seq检测。加权基因共表达网络分析（WGCNA）确定了与暴露最相关的模块。利用相关分析、p值分析和富集分析对枢纽基因进行鉴定。利用支持向量机-递归特征消除（SVM-RFE）和最小绝对收缩和选择算子（LASSO）回归识别关键基因，然后利用单基因GSEA进行富集。构建了竞争性内源RNA （ceRNA）网络，并利用qRT-PCR进行了验证。与未暴露部位相比，430种mrna、168种lncrna和136种mirna在暴露部位的皮肤中差异表达。WGCNA从该模块的71个基因中鉴定出了MEthistle模块和12个交叉基因。这些富集的通路与肌肉有关。关键基因为KLHL41、MYBPC2和ERAP2。单基因GSEA鉴定了Hippo信号通路、基底细胞癌、细胞粘附分子等通路。与关键基因相关的6个mirna和18个lncrna组成了ceRNA网络，并通过qPCR进行了验证。利用免疫组织化学方法验证KLHL41、MYBPC2和ERAP2在蛋白水平上的差异表达。KLHL41、MYBPC2和ERAP2基因与皮肤光老化有关。基于这三个关键基因的光老化预测模型可以预测光老化。这些关键基因可能通过调节细胞生长、细胞间粘附和物质代谢途径在皮肤光老化中发挥作用。
Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation,p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways.