<i>In Silico</i> Identification of MicroRNAs Targeting Epidermal Growth Factor Receptor in the Initiation and Progression of Hepatocellular Carcinoma

Objectives Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. The epidermal growth factor receptor (EGFR) signalling pathway plays a vital role in the progression of HCC by influencing cell proliferation, survival, and resistance to apoptosis. This study aimed to identify the microRNAs (miRNAs) that regulate EGFR signalling in HCC using in silico approaches. Material and Methods The differential expression of EGFR and its correlation with patient survival in HCC were first established by analysing relative gene expression and overall survival using the University of Alabama at Birmingham Cancer (UALCAN) data analysis portal. Further, EGFR-associated genes and the regulatory transcription factors (TFs) were identified through STRING and Network Analyst tools, respectively. The protein–protein interaction (PPI) network of EGFR-associated genes was then constructed using Cytoscape. The differentially expressed miRNAs (DE-miRNAs) in HCC were identified by analysing the GSE dataset GSE147889 using the GEO2R tool. The miRWalk database was extensively mined to predict miRNAs targeting EGFR and its associated genes. Finally, a regulatory network was built to map the interactions between the miRNAs, TFs, and EGFR-associated genes. Results The UALCAN analysis revealed that EGFR is downregulated in liver carcinoma, but there is no significant correlation with patient survival. The PPI network analysis identified 21 critical genes and 30 TFs involved in EGFR regulation. Among the 18 differentially expressed miRNAs, hsa-miR-216 b-5p, hsa-miR-214-3p, hsa-miR-325, hsa- miR-199a/b-3p, and hsa-miR-200a-3p were identified as key regulators of EGFR expression. Furthermore, the regulatory network analysis revealed that 15 DE-miRNAs regulate EGFR by targeting 14 EGFR-associated genes and interacting with 23 TFs. Conclusion This in silico study identifies hsa-miR-216b-5p, hsa-miR-214–3p, hsa-miR-325, hsa-miR-199a-3p, hsa-miR-200a-3p, and hsa-miR-199b-3p as hub miRNAs regulating EGFR in HCC. Although further experimental validation is required, these miRNAs may have the potential to develop as diagnostic or prognostic markers, as well as therapeutic targets, in the management of liver carcinomas.