Potential Roles of Long Non-Coding RNAs in Regulating Cell Proliferation, Invasion, and Metastasis in Ovarian Serous Cystadenocarcinoma

Abstract

\n Background: Ovarian serous cystadenocarcinoma (OSC) is the most common gynecological malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and involved in cell proliferation, apoptosis, angiogenesis, and invasion. Here, we investigated the functional roles of lncRNAs in OSC in detail.Methods: We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas and used differentially expressed lncRNAs and mRNAs to construct an lncRNA-mRNA co-expression network. Distinct lncRNAs were classified into lincRNA, enhancer-like lncRNAs, or antisense lncRNAs. Biological functions for lncRNAs were predicted according to the lncRNA-mRNA network and genomic adjacency by KEGG pathway analysis. A transcription factor (TF)-lncRNA regulatory network was constructed by integrating lncRNA molecular profiles and TF binding information. Results: We identified 2,939 lncRNAs and 2,766 mRNAs that were differentially expressed between OSC and normal ovary tissues. The 67 lncRNAs in the lncRNA-mRNA network, 23 lincRNAs, 19 antisense lncRNAs, and four enhancer-like lncRNAs were involved in cell proliferation, invasion, and metastasis. The TFs ING4, TTF-1, RUSH-l alpha, Kaiso, and STAT1 targeted regulation of lncRNAs in the pathological processes of OSC. Expression of 10 lncRNAs and mRNAs, as well as SOS1, ITGB1, and BIRC2 mRNAs with their identified lncRNAs were verified by qRT-PCR in OSC tissues. Conclusion: We predicted the biological functions of many lncRNAs, which may serve as diagnostic and prognostic biomarkers as well as therapeutic targets in OSC.