子宫内膜异位症在位内膜中自噬相关基因及ceRNA网络的作用

Effect of autophagy-related genes and ceRNA network in endometriosis eutopic endometrium

目的通过筛选子宫内膜异位症在位内膜中的自噬相关基因,明晰竞争性内源性RNA(ceRNA)网络在子宫内膜异位症中的作用.方法从GEO数据库和Human Autophagy Database数据库分别获取子宫内膜异位症数据集和自噬相关基因列表,查找自噬相关基因,通过预测和相关性筛选miRNA和LncRNA并构建ceRNA网络.验证筛选得到的关键基因在其他子宫内膜异位症在位内膜数据集的表达及诊断效能.结果子宫内膜异位症在位内膜中有39个自噬相关基因存在表达差异,通过PPI查找到7个关键基因,功能富集在巨自噬、线粒体自噬和激活转录因子等,信号通路主要涉及E2F、FOXO、DNA损伤修复、FAS信号通路、PI3K/Akt/mTOR等.构建11个ceRNA调控网络,包括4个mRNA(CASP3、HIF1A、CDKN1A、RPS6KB1)、7个miRNA(hsa-let-7e-5p、hsa-miR-124-3p、hsa-miR-199a-5p、hsa-miR-200c-3p、hsa-miR-24-3p、hsa-miR-30a-5p和hsa-miR-382-5p)和8个LncRNA(NORAD、TUG1、MALAT1、CYTOR、PVT1、EBLN3P、LINC02381和XIST).结论自噬相关基因参与的ceRNA网络调控关系,可以为我们研究子宫内膜异位症诊断和治疗靶点提供新的方向.

Objective The goal of this study was to identify the crucial autophagy-related genes in endometriosis and construct the competitive endogenous RNA(ceRNA) to further understand the pathogenesis of endometriosis.Methods Gene Expression Omnibus(GEO) database and Human Autophagy Database(HADb) were used to identify differentially expressed mRNAs, then the related miRNAs and lncRNAs were predicted through software to construct a ceRNAs network.At the same time, another endometriosis dataset was analyzed to confirm the levels of crucial mRNAs expression and ROC in the ceRNA network.Results The differential expression analysis revealed 39 differentially expressed autophagy-related genes.Seven hub genes were found by PPI,which had high diagnostic performance.The functions of 7 hub genes were enriched in macroautophagy, mitophagy and activating transcription factors etc.The signaling pathways mainly involved E2F,FOXO,DNA damage repair, FAS signaling pathway, PI3K/Akt/mTOR.11 ceRNA networks consisting of 4 mRNAs(CASP3,HIF1A,CDKN1 Aand RPS6 KB1),7 miRNAs(hsa-let-7e-5p, hsa-miR-124-3p, hsa-miR-199a-5p, hsa-miR-200c-3p, hsa-miR-24-3p, hsa-miR-30a-5p and hsa-miR-382-5 p), and 8 lncRNAs(NORAD,TUG1,MALAT1,CYTOR,PVT1,EBLN3 P,LINC02381 and XIST) were constructed.Conclusion The ceRNA network regulatory relationship involving autophagy-related genes can provide new directions to study the diagnostic and therapeutic targets of endometriosis.