通过构建ceRNA网络探索子宫内膜异位症潜在的关键长链非编码RNA
Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network.
作者信息
Gu Chenglei, Meng Yuanguang, Meng Qingqing, Fan Wensheng, Ye Mingxia, Zhang Qian, Zhang Nina, Li Lian
机构信息
Department of Obstetrics and Gynecology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.
Health Care Office, Agency for Offices Administration of Central Military Commission of People's Republic of China, Beijing, People's Republic of China.
出版信息
Int J Gen Med. 2021 Aug 5;14:4161-4170. doi: 10.2147/IJGM.S321648. eCollection 2021.
PURPOSE
The etiology and pathophysiology of endometriosis remain unclear. Current research indicates long noncoding RNA (lncRNA) may play an important role in the pathogenesis and development of endometriosis. However, the molecular mechanism of lncRNA in endometriosis is far from clear.
PATIENTS AND METHODS
The lncRNA and mRNA expression of 8 patients with ovarian endometriosis were determined by high-throughput RNA sequencing (8 ectopic endometria samples vs 8 eutopic endometria samples), and miRNA expression profiles were obtained from our previous study. Then a lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by combining the regulatory interaction and negative co-expression interaction between the differentially expressed lncRNAs/mRNAs and miRNAs by different rules.
RESULTS
The constructed lncRNA-related ceRNA network was composed of two separate networks, network 1 including 14,137 dysregulated lncRNA-mRNA interactions, referring to 242 lncRNAs, 55 miRNAs and 1600 mRNAs, network 2 including 4459 dysregulated lncRNA-mRNA interactions, referring to 111 lncRNAs, 39 miRNAs and 1151 mRNAs. The top six hub lncRNAs (LINC01140, MSC-AS1, HAGLR, CKMT2-AS1, JAKMIP2-AS1, AL365361.1) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 1, and the top six hub lncRNAs (PAX8-AS1, MIR17HC, PART1, HOXA-AS3, PLAC4, LINC00511) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 2 were selected. Functional enrichment analysis of these lncRNA-related mRNAs indicated that the lncRNAs in network 1 mainly take part in positive regulation of phagocytosis, myeloid leukocyte activation, and tissue remodeling, while the lncRNAs in network 2 mainly take part in negative regulation of cell proliferation, blood vessel development and regulation of epithelial cell differentiation, which is consistent with the results obtained from the different rules to construct the networks.
CONCLUSION
lncRNA-related ceRNA network analysis recognized key lncRNAs related to the development of endometriosis.
目的
子宫内膜异位症的病因和病理生理学仍不清楚。目前的研究表明，长链非编码RNA（lncRNA）可能在子宫内膜异位症的发病机制和发展中起重要作用。然而，lncRNA在子宫内膜异位症中的分子机制尚不清楚。
患者和方法
通过高通量RNA测序确定8例卵巢子宫内膜异位症患者的lncRNA和mRNA表达（8个异位内膜样本与8个在位内膜样本），并从我们之前的研究中获得miRNA表达谱。然后，通过不同规则结合差异表达的lncRNAs/mRNAs与miRNAs之间的调控相互作用和负共表达相互作用，构建lncRNA相关的竞争性内源性RNA（ceRNA）网络。
结果
构建的lncRNA相关ceRNA网络由两个独立的网络组成，网络1包括14137个失调的lncRNA-mRNA相互作用，涉及242个lncRNAs、55个miRNAs和1600个mRNAs，网络2包括4459个失调的lncRNA-mRNA相互作用，涉及111个lncRNAs、39个miRNAs和1151个mRNAs。选择网络1中mRNA-miRNA-lncRNA显著三元关系中的前六个枢纽lncRNAs（LINC01140、MSC-AS1、HAGLR、CKMT2-AS1、JAKMIP2-AS1、AL365361.1），以及网络2中mRNA-miRNA-lncRNA显著三元关系中的前六个枢纽lncRNAs（PAX8-AS1、MIR17HC、PART1 HOXA-AS3、PLAC4、LINC00511）。对这些与lncRNA相关的mRNAs进行功能富集分析表明，网络1中的lncRNAs主要参与吞噬作用的正调控、髓系白细胞活化和组织重塑，而网络2中的lncRNAs主要参与细胞增殖的负调控、血管发育和上皮细胞分化的调控，这与构建网络的不同规则所获得的结果一致。
结论
lncRNA相关ceRNA网络分析识别出与子宫内膜异位症发展相关的关键lncRNAs。
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