Investigation of the clinical significance and molecular mechanism of miR-21-5p in hepatocellular carcinoma: A systematic review based on 24 studies and bioinformatics investigation

To investigate the prospective roles and the clinicopathological application of microRNA-21-5p (miR-21-5p) in hepatocellular carcinoma (HCC), the present review is based on 24 studies and bioinformatics investigation. Firstly, HCC-associated miR-21-5p data were aggregated from literature databases and two public genomic data repositories, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Potential target genes of miR-21-5p in HCC were identified using TCGA and GEO, Natural Language Processing and 14 online software packages. The oncogenic roles of these target genes was probed for understanding using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Hub genes were further investigated by protein-protein interaction network (PPI) analysis. Comprehensive meta-analysis, including 10 microarrays from GEO datasets, 13 literature studies and TCGA-based RNA sequencing data, indicated a reliable diagnostic capacity of miR-21-5p [area under the curve (AUC), 0.887; sensitivity, 0.78% and specificity, 0.79%]. The healthy control group (AUC, 0.926; sensitivity, 0.87% and specificity, 0.82%) demonstrated high diagnostic capacity of miR-21-5p compared with the chronic hepatitis B infection group (AUC, 0.904; sensitivity, 0.75% and specificity, 0.84%). A total of 10 significant enrichment pathways were indicated by KEGG analysis, with cytokine-cytokine receptor interaction exhibiting the highest score. A total of 5 genes, hepatocyte growth factor, forkhead box O1 (FOXO1), thrombospondin 1, estrogen receptor 1 (ESR1) and C-X-C motif chemokine ligand 12 were selected from 39 overlapping genes, according to the PPI network. Target genes were assembled in GO terms associated with ‘response to chemical stimulus’, ‘cell surface’ and ‘growth factor binding’. In particular, low expression of FOXO1 and ESR1 was associated with miR-21-5p expression. In conclusion, upregulated expression of miR-21-5p may be a functional regulator of the metabolism or apoptosis in HCC and a novel tumor marker for the early diagnosis of HCC.