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

  • NPJ Aging. 2025 Dec 17;11(1):101. doi: 10.1038/s41514-025-00294-1.
Christopher Ren  1 ,  Geoffrey Ho Duen Leung  2 ,  Qiuqiong Tang  3 ,  Peiran Zhang  3 ,  Yongming Ma  3 ,  Ying Xin  2 ,  Sarah Wing Yan Lok  2 ,  Frank W Pun  4 ,  Alex Zhavoronkov  5  6
Affiliations
  • 1. Shanghai High School International Division, Shanghai, China.
  • 2. Insilico Medicine Hong Kong Ltd, Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park, Hong Kong SAR, China.
  • 3. Insilico Medicine Suzhou Ltd, Suzhou, Jiangsu, China.
  • 4. Insilico Medicine Hong Kong Ltd, Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park, Hong Kong SAR, China. [email protected].
  • 5. Insilico Medicine Hong Kong Ltd, Unit 310, 3/F, Building 8W, Hong Kong Science and Technology Park, Hong Kong SAR, China. [email protected].
  • 6. Insilico Medicine US Inc, Cambridge, MA, USA. [email protected].
PMID: 41407697 DOI: 10.1038/s41514-025-00294-1
Abstract

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.

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