Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2026年4月20日

查看全文
  • Tomohiko Ikehara,
  • Hajime Otsu,
  • Taro Tobo,
  • Kiyotaka Hosoda,
  • Kosuke Hirose,
  • Takashi Ofuchi,
  • Akinori Tsujimoto,
  • Shohei Shibuta,
  • Koto Kawata,
  • Shinsaku Itoyama,
  • Kazuki Omachi,
  • Yu Takahashi,
  • Yushi Motomura,
  • Yoshiki Hiraki,
  • Yuki Ando,
  • Qingjiang Hu,
  • Yusuke Yonemura,
  • Akira Shimizu,
  • Takaaki Masuda,
  • Yuji Soejima,
  • Koshi Mimori

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.