Novel driver gene FIRRM regulates the cell cycle for promoting tumor growth in hepatocellular carcinoma

Abnormalities in the cell cycle are fundamental mechanisms underlying tumor progression in hepatocellular carcinoma (HCC). Therapeutic strategies targeting mutations or abnormal activation of genes and pathways associated with cell cycle control are under development. However, the efficacy of cell cycle-targeted therapies is currently limited; therefore, identifying additional biomarkers and therapeutic targets is necessary.

Copy number variation was analyzed using The Cancer Genome Atlas dataset for identifying FIRRM (fidgetin-like 1-interacting regulator of recombination and mitosis) as a potential driver of HCC development, and evaluating its clinical significance. Furthermore, the biological significance of FIRRM in HCC was validated using in vitro and in vivo studies involving FIRRM-knockout HCC cell lines.

FIRRM is located on amplified chromosome 1q and exhibits elevated expression in tumor cells. It was identified as an independent poor prognostic factor in patients with HCC, and immunohistochemical staining revealed that it was primarily localized in the cytoplasm and membranes of HCC cells. FIRRM knockout suppressed HCC cell proliferation, reduced polo-like kinase 1 (PLK1) phosphorylation, and inhibited mitotic progression and the G2-to-M transition of the cell cycle. Furthermore, FIRRM knockout inhibited tumor proliferation in vivo.

FIRRM was identified as a novel driver gene in HCC, which accelerated tumor proliferation through PLK1-mediated mitotic progression and promotion of the G2/M transition. These findings suggest that FIRRM is a promising target for HCC therapy.