LINC01018 和 SMIM25 通过 ceRNA 网络构建揭示了子宫内膜异位症中的 miR-182-5p 海绵作用。
LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction.
机构信息
Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
出版信息
Int J Immunopathol Pharmacol. 2020 Jan-Dec;34:2058738420976309. doi: 10.1177/2058738420976309.
The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples.LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.
本研究旨在探讨在子宫内膜异位症（EMs）竞争内源性 RNA（ceRNA）网络背景下长链非编码 RNA（lncRNA）、微小 RNA（miRNA）和信使 RNA（mRNA）之间的相互作用。基于三个 RNA-seq 数据集（GSE105765、GSE121406 和 GSE105764），鉴定了 EMs 异位（EC）和在位（EU）子宫内膜中差异表达的 miRNA（DEmiRs）、差异表达的 lncRNA（DELs）和差异表达的基因（DEGs），用于构建 ceRNA 网络。然后，对 ceRNA 网络中的 DEGs 进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路和蛋白质-蛋白质相互作用（PPI）分析。此外，在 GSE124010 中验证了 ceRNA 网络中的 DEmiRs。并在 GSE86534 中验证了 ceRNA 网络中验证的 DEmiRs 的靶 DELs 和 DEGs。探讨了验证的 DEmiRs、DEGs 和 DELs 之间的相关性。此外，还应用基因集富集分析（GSEA）研究了验证的 DEmiRs、DEGs 和 DELs 的功能。总体而言，从 GSE105764 中获得了 1352 个 DEGs 和 595 个 DELs，以及 GSE105765 和 GSE121406 之间的 27 个重叠的 DEmiRs。随后，构建了一个包含 11 个上调和 16 个下调的 DEmiRs、7 个上调和 13 个下调的 DELs、48 个上调和 46 个下调的 DEGs 的 ceRNA 网络。GO 和 KEGG 通路分析表明，该 ceRNA 网络可能与炎症相关途径有关。此外，hsa-miR-182-5p 及其靶 DELs（LINC01018 和 SMIM25）和 DEGs（BNC2、CHL1、HMCN1、PRDM16）在验证分析中得到了成功验证。此外，hsa-miR-182-5p 与这些靶 DELs 和 DEGs 呈显著负相关。GSEA 分析表明，在子宫内膜异位症 EU 样本中，LINC01018、SMIM25 和 CHL1 的高表达和 hsa-miR-182-5p 的低表达会激活炎症相关途径。LINC01018 和 SMIM25 可能通过海绵吸附 hsa-miR-182-5p 来上调下游基因，如 CHL1，从而促进子宫内膜异位症的发展。
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