In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma

• Published in: Genes Vol. 13; no. 12; p. 2343
• Main Authors: Abd ElAziz, Omnia Nasser, Elfiky, Asmaa M, Yassin, Mohamed A, Abd El-Hakam, Fatma El-Zahraa, Saleh, Eman M, El-Hefnawi, Mahmoud, Mohamed, Rania Hassan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: Animals; Bioinformatics; Breast cancer; Carcinoma, Hepatocellular - pathology; Cloning; Development and progression; Fbxl3; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Hep G2 Cells; Hepatocellular carcinoma; Hepatoma; Humans; Liver cancer; Liver Neoplasms - pathology; Medical prognosis; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-181c-5p; miRNA; nano-delivery; oncogenic miRNA; Pathogenesis; Tumors; Egypt; United States > US; Basel Switzerland; Switzerland; miR-181c-5p; nano-delivery; Fbxl3; hepatocellular carcinoma; oncogenic miRNA
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13122343

Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75-85% of primary liver cancers. The conclusive research on miR-181c-5p's role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC development, but also confirmed the fluctuating data around its role. miR-181c-5p was proven here to have an oncogenic role by increasing HepG2 cells' viability as confirmed by MTT analysis. In addition, miR-181c-5p was upregulated in the HCC positive control group and progressed the HCC development and malignant features by its forced expression in an HCC mouse model by targeted delivery using a LA-PAMAM polyplex. This is indicated by the cancerous gross and histological features, and the significant increase in liver function biomarkers. The functional enrichment bioinformatics analyses of miR-181c-5p-downregulated targets in HCC indicated that miR-181c-5p targets were significantly enriched in multiple pathways and biological processes involved in HCC development. Fbxl3, an example for miR-181c-5p potential targets, downregulation and its correlation with miR-181c-5p were validated by qPCR. In conclusion, miR-181c-5p is upregulated in HCC and has an oncogenic role enhancing HCC progression.