Construction of a miRNA-mRNA network related to exosomes in metastatic hepatocellular carcinoma

Aims: This study aimed to construct a miRNA-mRNA network to elucidate the molecular mechanism of exosome function in metastatic HCC. Methods: We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 50 samples to obtain differentially expressed miRNAs (DEMs) and mRNAs (DEGs) involved in the progression of metastatic HCC. Next, a miRNA-mRNA network related to exosomes in metastatic HCC was constructed on the basis of the identified DEMs and DEGs. Finally, the function of the miRNA-mRNA network was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Immunohistochemistry was performed to validate expression of NUCKS1 in HCC specimens. Based on the immunohistochemistry, the score of the NUCKS1 expression was calculated, and the patients were divided into high- and lowexpression patients, and the differences in survival between the two groups were compared. Results: Through our analysis, 149 DEMs and 60 DEGs were identified. In addition, a miRNAmRNA network, including 23 miRNAs and 14 mRNAs, was constructed. Low expression of NUCKS1 was validated in the majority of HCCs compared with their matched adjacent cirrhosis specimens (P < 0.001), which was consistent with our result of differential expression analyses. HCC patients with low expression of NUCKS1 had shorter overall survival than those with high NUCKS1 expression (P = 0.0441). Conclusions: The novel miRNA-mRNA network will provide new insights into the underlying molecular mechanisms of exosomes in metastatic HCC. NUCKS1 might serve a potential therapeutic target to restrain the development of HCC.

Automated summary

This study aimed to construct a miRNA-mRNA network to elucidate the molecular mechanism of exosome function in metastatic HCC. Through analyzing RNA samples from 50 cases, 149 DEMs and 60 DEGs involved in the progression of metastatic HCC were identified and a miRNA-mRNA network related to exosomes was constructed. The low expression of NUCKS1 in HCC was validated, and HCC patients with low expression of NUCKS1 had shorter overall survival. The findings provide new insights into the underlying molecular mechanisms of exosomes in metastatic HCC and suggest NUCKS1 as a potential therapeutic target.