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Updated: Jul 5, 2025

Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation
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Published on: August 23, 2018

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NAT10 mediated ac4C acetylation driven m6A modification via involvement of YTHDC1-LDHA/PFKM regulates glycolysis and

Zhongting Mei1, Zhihua Shen2,3, Jiaying Pu2,3

  • 1Department of Pharmacology, (The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.

Cell Communication and Signaling : CCS
|January 17, 2024
PubMed

Insights

The enzyme NAT10 regulates RNA N4-acetylcytidine (ac4C) modification, impacting cancer progression. Inhibiting NAT10 enhances RNA N6-methyladenosine (m6A) levels, suppressing osteosarcoma growth and glycolysis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Dynamic RNA modifications like m6A are crucial in cancer, but upstream regulators remain underexplored.
  • The role of N4-acetylcytidine (ac4C) acetylation enzyme NAT10 in osteosarcoma and its link to m6A modification are investigated.

Discussion:

  • NAT10 knockdown increases m6A levels, suppressing osteosarcoma cell proliferation, migration, and invasion.
  • NAT10 regulates the stability and translation of the m6A reader protein YTHDC1.
  • YTHDC1 influences glycolysis by recognizing m6A sites on PFKM and LDHA mRNAs, affecting their stability.

Key Insights:

  • A novel signaling axis: NAT10/ac4C-YTHDC1/m6A-LDHA/PFKM positively regulates cancer cell glycolysis.
  • NAT10 inhibition suppresses osteosarcoma progression by modulating m6A-dependent glycolysis.
  • YTHDC1 partially rescues NAT10 knockdown effects, confirming its role in the pathway.

Outlook:

  • Targeting the NAT10/ac4C-YTHDC1 axis offers potential therapeutic strategies for osteosarcoma.
  • Further research can elucidate the precise mechanisms of ac4C and m6A crosstalk in cancer.
  • Exploring YTHDC1's role in other cancers could reveal broader therapeutic applications.
Keywords:
GlycolysisLDHANAT10OsteosarcomaPFKMYTHDC1ac4C acetylationm6A methylation

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