Bioinformatic analysis and prediction of the function and regulatory network of long non-coding RNAs in hepatocellular carcinoma

Abstract

Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases. HCC-associated lncRNAs, including HOX antisense intergenic RNA (HOTAIR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were selected based on established databases of lncRNAs. The interaction between the HCC-associated lncRNAs and miRNAs (hsa-miR-1, hsa-miR-20a-5p) was predicted using starBase2.0. Signal transducer and activator of transcription 1, hepatocyte nuclear factor 4α (HNF4A), octamer-binding transcription factor 4, Nanog homeobox (NANOG), caudal type homeobox 2 (CDX2), DEAD-box helicase 5, brahma-related gene 1, MYC-associated factor X and MYC proto-oncogene, bHLH transcription factor have been identified as the transcription factors for HOTAIR and MALAT1 using ChIPBase. Additionally, CDX2, HNF4A, NANOG, ETS transcription factor, Jun proto-oncogene and forkhead box protein A1 were identified as the transcription factors for hsa-miR-1 and hsa-miR-20a-5p. CDX2, HNF4A and NANOG were the transcriptional factors in common between the lncRNAs and miRNAs. Cyclin D1, E2F transcription factor 1, epithelial growth factor receptor, MYC, MET proto-oncogene, receptor tyrosine kinase and vascular endothelial growth factor A were identified as target genes for the HCC progression, two of which were also the target genes of hsa-miR-1 and hsa-miR-20a-5p using the miRwalk and OncoDN. HCC databases. Additionally, these target genes may be involved in biological functions, including the regulation of cell growth, cell cycle progression and mitosis, and in disease progression, as demonstrated using DAVID clustering analysis. The present study aimed to predict a regulatory network of lncRNAs in HCC progression using bioinformatics analysis.