PRMT5 Mediated HIF1α Signaling and Ras-Related Nuclear Protein as Promising Biomarker in Hepatocellular Carcinoma

• Published in: Biology (Basel, Switzerland) Switzerland), 2024-04, Vol.13 (4), p.216
• Main Authors: Abumustafa, Wafaa, Castven, Darko, Sharif-Askari, Fatemeh Saheb, Abi Zamer, Batoul, Hamad, Mawieh, Marquardt, Jens-Uwe, Muhammad, Jibran Sualeh
• Format: Article
• Language: English
• Subjects: Analysis; Biomarkers; Cell cycle; Consortia; CpG islands; Development and progression; Disease; DNA methylation; Drug resistance; Epigenetic inheritance; Epigenetics; Gene expression; Genes; Genomes; Health aspects; Hepatitis; Hepatocellular carcinoma; Hepatoma; HIF1α; Hypoxia; Liver; Liver cancer; Medical prognosis; Methylation; N-Methyltransferase; Patients; protein arginine N-methyltransferase 5; Proteins; Ras protein; Ras-related nuclear protein; Signal transduction; Survival analysis; Therapeutic targets; Transcriptomes; Transferases
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology13040216

Protein arginine N-methyltransferase 5 (PRMT5) has been identified as a potential therapeutic target for various cancer types. However, its role in regulating the hepatocellular carcinoma (HCC) transcriptome remains poorly understood. In this study, publicly available databases were employed to investigate PRMT5 expression, its correlation with overall survival, targeted pathways, and genes of interest in HCC. Additionally, we utilized in-house generated NGS data to explore expression in dysplastic nodules compared to hepatocellular carcinoma. Our findings revealed that PRMT5 is significantly overexpressed in HCC compared to normal liver, and elevated expression correlates with poor overall survival. To gain insights into the mechanism driving overexpression in HCC, we analyzed promoter CpG islands and methylation status in HCC compared to normal tissues. Pathway analysis of knockdown in the HCC cells revealed a connection between expression and genes related to the HIF1α pathway. Additionally, by filtering PRMT5-correlated genes within the HIF1α pathway and selecting up/downregulated genes in HCC patients, we identified Ras-related nuclear protein (RAN) as a target associated with overall survival. For the first time, we report that PRMT5 is implicated in the regulation of and genes, suggesting the potential prognostic utility of PRMT5 in HCC.