| Autor: |
Abumustafa W; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Castven D; First Medical Department, University Medical Center Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany., Sharif-Askari FS; Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates., Abi Zamer B; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Hamad M; Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates., Marquardt JU; First Medical Department, University Medical Center Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany., Muhammad JS; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.; Research Institute of Medical and Health Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. |
| Abstrakt: |
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 PRMT5 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 PRMT5 overexpression in HCC, we analyzed promoter CpG islands and methylation status in HCC compared to normal tissues. Pathway analysis of PRMT5 knockdown in the HCC cells revealed a connection between PRMT5 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 HIF1A and RAN genes, suggesting the potential prognostic utility of PRMT5 in HCC. |
