Reducing protein regulator of cytokinesis 1 as a prospective therapy for hepatocellular carcinoma

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Microtubule-binding proteins play crucial roles in the cell cycle.
• Some microtubule-associated proteins exhibit oncogenic properties, but their mechanisms in cancer are not fully understood.
• Hepatocellular carcinoma (HCC) is a significant global health concern with complex underlying molecular mechanisms.

Purpose of the Study:

• To investigate the role of Protein Regulator of Cytokinesis 1 (PRC1) in human hepatocellular carcinoma (HCC).
• To explore the therapeutic potential of targeting PRC1 in combination with microtubule-associated agents (MTAs) for HCC treatment.

Main Methods:

• Quantitative analysis of PRC1 expression in HCC tissues.
• In vitro studies involving siRNA-mediated PRC1 knockdown in HCC cell lines.
• Assessment of cell cycle progression, mitotic exit, and apoptosis.
• In vivo studies using subcutaneous and orthotopic HCC xenograft mouse models.
• Evaluation of synergistic effects between PRC1 inhibition and taxol treatment.

Main Results:

• PRC1 is overexpressed in HCC and associated with poorer patient survival.
• Reducing PRC1 levels blocks mitotic exit in HCC cells at telophase, independently of the spindle assembly checkpoint.
• PRC1 inhibition synergizes with MTAs to suppress HCC cells, dependent on p53 or p14ARF status.
• Overexpression of PRC1 confers resistance to taxol in HCC.
• Combined taxol and shPRC1 treatment achieved 90% tumor growth suppression in xenograft models.
• Reducing PRC1 alleviated HCC development and hepatic injury in orthotopic mouse models.

Conclusions:

• PRC1 is an oncogenic protein in HCC, promoting proliferation and survival.
• Targeting PRC1, particularly in combination with MTAs like taxol, represents a promising dual-mitotic suppression strategy for HCC.
• This approach effectively inhibits HCC at both metaphase and telophase, offering a novel therapeutic avenue.