VIRMA/IGF2BP3-mediated ANLN upregulation promotes intrahepatic cholangiocarcinoma growth by forming a positive

Jiajun Zhang1, Ning Huang1, Lin-Rui Gao2

  • 1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cell Death & Disease
|January 9, 2026
PubMed

Insights

Anillin (ANLN) drives intrahepatic cholangiocarcinoma (ICC) growth by regulating cell division and the Hippo pathway. Targeting ANLN with drugs like simvastatin or verteporfin shows promise for treating ICC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis due to limited targeted therapies.
  • Understanding ICC's molecular pathogenesis is crucial for developing effective treatments.
  • The role of anillin (ANLN), a cytoskeleton protein, in ICC is not well understood.

Purpose of the Study:

  • To investigate the role and regulatory mechanisms of ANLN in ICC.
  • To identify ANLN as a potential therapeutic target for ICC.
  • To explore the interplay between ANLN, RhoA signaling, and the Hippo pathway in ICC.

Main Methods:

  • Integrated bioinformatic analyses using spindle-related genes.
  • In vitro functional studies including gene knockdown and cell-based assays.
  • Analysis of clinical ICC cohorts to assess prognostic and predictive values.

Main Results:

  • ANLN is upregulated in ICC and correlates with worse survival.
  • VIRMA-mediated m6A modification and IGF2BP3 stabilize ANLN mRNA.
  • ANLN promotes ICC proliferation, cell cycle progression, and restrains the Hippo pathway via RhoA activation.
  • A self-reinforcing loop exists between ANLN and the Hippo pathway, regulated by RhoA signaling.
  • Simvastatin and verteporfin inhibit ICC growth by disrupting this signaling axis.

Conclusions:

  • ANLN plays a critical role in ICC progression by influencing cytokinesis and the Hippo pathway.
  • Combined detection of ANLN, VIRMA, or IGF2BP3 enhances ICC prediction.
  • Targeting the ANLN-mediated signaling axis with existing drugs offers a potential therapeutic strategy for ICC.

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