Upregulation of long non-coding RNA FOXP4-AS1 and its regulatory network in hepatocellular carcinoma

Objective: FOXP4-AS1 (FOXP4 antisense RNA 1) is putatively a functional oncogene in colorectal cancer. This study constructed a regulatory network involving FOXP4-AS1 for better understanding of its function in hepatocellular carcinoma (HCC). Methods: FOXP4-AS1 was assessed in HCC and adjacent normal (control) liver samples via quantitative real-time PCR. Differentially expressed micro RNAs (DEmiRNAs) were predicted. Their target genes were verified via the gene expression profiling interaction analysis (GEPIA) database, and subjected to gene ontology (GO) annotation and KEGG (Kyoto Encyclopedia of Genes and Genome) pathway enrichment analysis. Protein-protein interaction (PPI) networks were established and hub genes identified with Cytoscape software. The GEPIA database was used to assess the prognostic roles of 20 hub genes in liver cancer. The cBioPortal database was used to exhibit alterations of the genes. Results: The HCC samples had significantly higher levels of FOXP4-AS1 compared with the control (P=0.001). Six upregulated and 4 downregulated DEmiRNAs were identified. Over-and under-expressed predicted target genes (183 and 147, respectively) were selected for GO annotation and KEGG pathway enrichment analysis. The downregulated genes were significantly prominent in the PI3K-Akt signaling pathway; the upregulated genes in the cell cycle. The PPI networks indicated IGFBP3 and PRC1 as hub genes with the highest node degrees. Higher expressions of 9 (6) genes were associated with worse (better) prognosis in HCC. Conclusion: An HCC-associated FOXP4-AS1-miRNA-mRNA regulatory network was constructed, and molecular mechanisms involved in HCC development were elucidated. This work provides direction for finding new HCC therapeutic targets.