AI-aided identification of dual-purpose therapeutic targets PRPF19 and MAPK9 in hepatocellular carcinoma and cellular senescence

Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant forms of primary liver cancer, with limited therapeutic options and a poor prognosis. Cellular senescence contributes to the progression of chronic liver disease while creating a microenvironment that supports tumor growth. This study aims to identify dual-purpose therapeutic targets for HCC treatment and cellular senescence intervention, potentially leading to more effective therapeutic strategies. Utilizing the AI-driven target discovery platform PandaOmics, we prioritized 27 high-confidence, and 8 novel HCC targets potentially associated with cellular senescence. Experimental validations confirmed that the knockdown of pre-mRNA-processing factor 19 (PRPF19) or mitogen-activated protein kinase 9 (MAPK9) in HCC cells significantly reduced cell proliferation. Additionally, suppression of PRPF19 or MAPK9 in hepatic stellate cells treated with doxorubicin resulted in a significant decrease in cellular senescence. These findings underscore the pivotal roles of PRPF19 and MAPK9 in both HCC cell proliferation and cellular senescence, suggesting them as promising novel dual-purpose therapeutic targets for HCC treatment and mitigation of senescence-associated pathologies.