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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月17日

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  • Christopher Ren,
  • Geoffrey Ho Duen Leung,
  • Qiuqiong Tang,
  • Peiran Zhang,
  • Yongming Ma,
  • Ying Xin,
  • Sarah Wing Yan Lok,
  • Frank W. Pun,
  • Alex Zhavoronkov

摘要

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.