Haytham Makki, Ki-Hoon Park, Ja-Eun Kim, Hwajin Lee, Ji Lee, Dong Yon, Young-Il Choi, Hyung-Joo Chung, Junyang Jung and Na Jeong
Background and Objective: Liver cirrhosis and hepatocellular carcinoma are significant global health challenges characterized by high morbidity and mortality rates. The RNA-binding proteins play critical roles in post-transcriptional gene regulation and are implicated in the pathogenesis of these conditions. This study aimed to identify and validate novel druggable RNA-binding proteins involved in liver cirrhosis and hepatocellular carcinoma progression. Materials and Methods: An integrated approach combining bioinformatics analysis and experimental validation was employed. The study involved data mining from the Gene Expression Omnibus database to identify upregulated genes. In vivo, validation was conducted via human liver tissue samples from patients with alcoholic cirrhosis and nonviral hepatocellular carcinoma. In vitro assays using human hepatoma cells were used to assess the effects of the compound alpha-naphthoflavone on cell viability and gene expressions. Results: A total of ten RNA-binding protein targets (HNRNPA1, HNRNPC, NONO, KHDRBS1, SRSF1, XRN2, YWHAZ, ANXA4, HDAC2 and ITGB1) were identified through overlap with RNA-binding protein databases. In experimental validation, the expression of these targets was significantly elevated in patient samples compared with the tumor-free controls. Treatment of hepatoma cells with alpha-naphthoflavone dose-dependently increased cell viability in a drug-induced liver injury model and downregulated the expression of oncogenic kinases and multiple RNA-binding proteins. Conclusion: These findings suggested that targeting RNA-binding proteins could lead to new therapeutic strategies that increase treatment efficacy and safety. Further investigations into the in vivo efficacy of alpha-naphthoflavone as a promising multitarget inhibitor are warranted.
Haytham Makki, Ki-Hoon Park, Ja-Eun Kim, Hwajin Lee, Ji Lee, Dong Yon, Young-Il Choi, Hyung-Joo Chung, Junyang Jung and Na Jeong, 2024. Identifying Druggable RNA-Binding Proteins for Liver Cirrhosis/HCC Treatment: Integrated Bioinformatics Analysis with Experimental Validation. International Journal of Pharmacology, 20: 1466-1478.