J Cancer 2020; 11(23):7057-7072. doi:10.7150/jca.49557 This issue

Research Paper

Construction of novel mRNA-miRNA-lncRNA regulatory networks associated with prognosis of ovarian cancer

Lingling Gao1,2, Xiao Li1,2, Xin Nie1,2, Qian Guo1,2, Qing Liu1,2, Yue Qi1,2, Juanjuan Liu1,2, Bei Lin1,2✉

1. Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.
2. Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Liaoning, China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Gao L, Li X, Nie X, Guo Q, Liu Q, Qi Y, Liu J, Lin B. Construction of novel mRNA-miRNA-lncRNA regulatory networks associated with prognosis of ovarian cancer. J Cancer 2020; 11(23):7057-7072. doi:10.7150/jca.49557. Available from https://www.jcancer.org/v11p7057.htm

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Graphic abstract

Background: Ovarian cancer (OC) is the most lethal malignancy in the female reproductive system. Growing evidences demonstrates that competing endogenous RNA (ceRNA) network play crucial roles in the occurrence and progression of tumors. Therefore, we aimed to explore and identify novel mRNA-miRNA-lncRNA ceRNA networks associated with prognosis of OC.

Methods: The differentially expressed gene (DEGs) of four expression profiles datasets (GSE5438, GSE40595, GSE38666 and GSE26712) were collected from Gene Expression Omnibus (GEO) database and analyzed with NetworkAnalyst. Intersection of DEGs were further employed for Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis. Protein-protein interaction (PPI) network and hub genes of DEGs were also identified. The expression levels and survival analysis of the hub genes in OC and their upstream miRNAs and lncRNAs were performed by various bioinformatics databases. More importantly, ceRNA networks were constructed based on mRNA-miRNA-lncRNA in OC.

Results: A total of 178 DEGs including 38 upregulated and 140 downregulated genes from intersected DEGs of four expression profiles were identified in OC. Functional enrichment analysis suggested that the commonly DEGs were enriched in regulating enzyme inhibitor activity, glycosaminoglycan and G protein-coupled receptor binding, cell morphogenesis, and involved in pathways including metabolic process, proteoglycans in cancer. Top 10 hub genes with higher connectivity degree were selected for subsequent expression and prognosis analysis. After take expression levels and prognostic roles of hub genes and their upstream miRNAs and lncRNAs in OC into consideration, 2 mRNAs (TACC3 and CXCR4), 2 miRNAs (hsa-miR-425-5p and hsa-miR-146a-5p) and 3 lncRNAs (FUT8-AS1, LINC00665 and LINC01535) were significantly associated with the poor prognosis of OC. The mRNA-miRNA-lncRNA networks (TACC3-hsa-miR-425-5p-FUT8-AS1 and CXCR4-hsa-miR-146a-5p-LINC00665/LINC01535) were eventually constructed in OC based on ceRNA mechanism.

Conclusion: We successfully constructed novel ceRNA network associated with the prognosis of ovarian cancer, which may provide a new strategy for early diagnosis and therapeutic intervention of OC.

Keywords: ovarian cancer, competing endogenous RNA, prognosis, bioinformatics analysis