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Published on: November 5, 2014

NAT10-Mediated ac4C Modification of circANKRD12 Reprograms the Tumor Microenvironment

Jiale Zhang1,2, Hui Shi2, Chen Wang2

  • 1Nanjing Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 22, 2026
PubMed

Insights

N4-acetylcytidine (ac4C) modification of circANKRD12 by NAT10 generates a protein that drives multiple myeloma (MM) proliferation and suppresses immune cells. The drug desloratadine targets this axis, offering a new strategy for MM treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Targeting both tumor growth and immune suppression is crucial for effective cancer therapy.
  • The role of circular RNA (circRNA) chemical modifications in cancer, particularly multiple myeloma (MM), is not well understood.

Purpose of the Study:

  • To investigate the role of N4-acetylcytidine (ac4C) modification in circANKRD12 and its impact on MM proliferation and immune evasion.
  • To identify therapeutic strategies targeting the circANKRD12 pathway in MM.

Main Methods:

  • Identified circANKRD12 as an ac4C substrate modified by NAT10 in MM.
  • Characterized the translation of ac4C-modified circANKRD12 into circANKRD12_354aa.
  • Investigated the interaction of circANKRD12_354aa with HDAC2 and its effect on c-Myc.
  • Assessed the transfer of circANKRD12 to NK cells and its effect on cytotoxicity.
  • Screened for drugs targeting circANKRD12_354aa and evaluated their efficacy in vivo.

Main Results:

  • ac4C modification promotes circANKRD12 translation into circANKRD12_354aa, which stabilizes c-Myc, driving MM proliferation.
  • circANKRD12 is transferred to NK cells, suppressing their cytotoxicity via the HDAC2/c-Myc pathway and promoting immune evasion.
  • circANKRD12 is upregulated in MM patients and associated with poor prognosis.
  • Desloratadine was identified as a direct binder of circANKRD12_354aa and effectively suppressed MM growth and restored NK cell immunity in vivo.

Conclusions:

  • NAT10-mediated ac4C modification of circANKRD12 is a key mechanism coordinating MM cell proliferation and immune dysfunction.
  • circANKRD12_354aa is a promising therapeutic target for MM, and desloratadine shows potential for restoring antitumor immunity.
Keywords:
N4‐acetylcytidineN‐acetyltransferase 10circANKRD12desloratadinemultiple myeloma

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