Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network

Chenglei Gu,1,* Yuanguang Meng,1,* Qingqing Meng,2 Wensheng Fan,1 Mingxia Ye,1 Qian Zhang,1 Nina Zhang,1 Lian Li1 1Department of Obstetrics and Gynecology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Health Care Office, Agency for Offices Administration of Central Military Commission of People’s Republic of China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian LiDepartment of Obstetrics and Gynecology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of ChinaTel +86-10-6693-8244Fax +86-10-6693-7516Email lilianpla121@163.comPurpose: 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.Keywords: endometriosis, endometrium, microRNAs, lncRNA, integrative analysis, ceRNA networ