Construction and Investigation of an LINC00284-Associated Regulatory Network in Serous Ovarian Carcinoma

Abstract

The low survival rate associated with serous ovarian carcinoma (SOC) is largely due to the lack of relevant molecular markers for early detection and therapy. Increasing experimental evidence has demonstrated that long noncoding RNAs (lncRNAs) are involved in cancer initiation and development, and a competitive endogenous RNA (ceRNA) hypothesis has been formulated. Therefore, the characterization of new lncRNA and lncRNA-related networks is crucial for early diagnosis and targeted therapy of SOC. Data on lncRNAs, mRNAs, and miRNAs with differential expression in SOC, compared to normal ovarian tissue, were obtained from the Gene Expression Omnibus (GEO) database. Data on lncRNA expression and clinical data in SOC were obtained from The Cancer Genome Atlas (TCGA). lncRNA-miRNA interactions were predicted by the miRBase database. Different online tools, i.e., TargetScan, RNA22, miRmap, microT, miRanda, StarBase, and PicTar, were cooperatively utilized to predict the mRNAs targeted by miRNAs. The plugin of BiNGO in Cytoscape and KOBAS 3.0 were used to conduct the functional and pathway enrichment analyses. The lncRNA, miRNAs, and mRNAs identified to be expressed at statistically significant and different levels between SOC and healthy fallopian tube tissues were further validated using qRT-PCR. A total of 4 lncRNAs (LINC00284, HAGLR, HCAT158, and BLACAT1) and 111 mRNAs were found to be upregulated in SOC tissues compared to normal tissues, based on the GEO database. LINC00284 was found to be highly expressed in SOC, in association with the upregulation of the transcription factor SOX9. The high LINC00284 expression was associated with poor prognosis and proved to be an independent risk factor in patients with SOC, based on TCGA database. The qRT-PCR validation results closely recapitulated the expression profiles and prognostic scores of the aforementioned bioinformatic analyses. The LINC00284-related ceRNA network was found to be associated with SOC carcinogenesis by biofunctional analysis. In conclusion, the LINC00284-related ceRNA network may provide valuable information on the mechanisms of SOC initiation and progression. Importantly, LINC00284 proved to be a new potential prognostic biomarker for SOC.