N6-methyladenosine-mediated EIF3H promotes anaplastic thyroid cancer progression and ferroptosis resistance by

Zeyu Zhang1, Di Zhou1, Xiangyuan Qiu1

  • 1Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410000, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410000, China.

PubMed

Insights

EIF3H deubiquitylates and stabilizes beta-catenin, promoting anaplastic thyroid cancer (ATC) progression and ferroptosis resistance. Targeting the EIF3H/beta-catenin axis offers a potential therapeutic strategy for ATC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Anaplastic thyroid cancer (ATC) has a poor prognosis and limited treatment options.
  • The Wnt/beta-catenin pathway is crucial in ATC, but regulatory mechanisms are not fully understood.
  • The role of the JAMM family of deubiquitinating enzymes in ATC is unknown.

Purpose of the Study:

  • To identify a novel deubiquitinating enzyme that regulates beta-catenin in ATC.
  • To elucidate the mechanism by which this enzyme affects beta-catenin stability and Wnt/beta-catenin signaling.
  • To investigate the therapeutic potential of targeting this enzyme in ATC.

Main Methods:

  • Correlation analysis between EIF3H and beta-catenin expression in ATC.
  • EIF3H knockdown experiments to assess effects on Wnt/beta-catenin signaling.
  • Biochemical assays to confirm interaction, deubiquitylation, and stabilization of beta-catenin by EIF3H.
  • Assessment of EIF3H's impact on ATC cell proliferation, invasion, and ferroptosis resistance.
  • Investigation of EIF3H's association with m6A modification and IGF2BP2.

Main Results:

  • EIF3H expression positively correlates with beta-catenin levels in ATC.
  • EIF3H knockdown inhibits the Wnt/beta-catenin pathway, reducing ATC cell proliferation and invasion.
  • EIF3H directly deubiquitylates and stabilizes beta-catenin by removing K48-linked ubiquitin chains.
  • EIF3H knockdown enhances ferroptosis sensitivity in ATC cells.
  • EIF3H dysregulation is linked to m6A modification and the m6A reader IGF2BP2.

Conclusions:

  • The EIF3H/beta-catenin axis promotes ATC progression and ferroptosis resistance via Wnt/beta-catenin signaling activation.
  • EIF3H acts as a deubiquitinating enzyme targeting beta-catenin.
  • The EIF3H/beta-catenin axis presents a potential diagnostic marker and therapeutic target for ATC.

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