Identification of aberrantly expressed lncRNA and the associated TF-mRNA network in hepatocellular carcinoma.

Abstract

Emerging evidence has indicated that long noncoding RNA (lncRNA) plays crucial roles in regulating hepatocellular carcinoma (HCC) progression. However, a comprehensive lncRNA-transcription factor (TF)-message RNA (mRNA) in HCC remains absent. The aim of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in HCC. GSE124535 dataset was downloaded from the Gene Expression Omnibus database. Limma package in R was conducted to analyze abnormally expressed lncRNAs (differentially expressed lncRNAs [DELs]) and mRNAs (differentially expressed genes). The prognostic roles of screened DELs in HCC were evaluated at GEPIA. The expression of DELs that correlated with overall survival of HCC patients was further validated using circlncRNAnet, GEPIA, and StarBase. LncRNA-TF-mRNA potential triplets in HCC were predicted by LncMAP. After that, lncRNA-TF-mRNA networks were established using Cytoscape. A total of 20 upregulated and 17 downregulated DELs were identified in HCC tissues compared with adjacent noncancerous tissues. Six out of 20 upregulated and 6 out of 17 downregulated DELs were identified have significant impact on the overall survival of HCC patients. Results in circlncRNAnet, GEPIA, and Starbase confirmed the expression level of DELs obtained from GSE124535. Finally, the LncRNA-TF-mRNA regulatory networks for upregulated and downregulated lncRNA were established based on these analyses results. Among these lncRNAs in the network, the aberrantly expression of lncRNAs including LINC00511, RP11-290F5.1, MIR4435-2HG, and CTC-537E7.3 in HCC was first time reported to date. In the study, potential LncRNA-TF-mRNA regulatory networks were identified, which will advance our understanding concerning the progression of HCC.