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Updated: Jun 4, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
08:56

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

10.9K

N6-methyladenosine in 28S rRNA promotes oncogenic mRNA translation and tyrosine catabolism

Binbin Chen1, Li Li2, Ying Huang3

  • 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.

Cell Reports
|December 31, 2024
PubMed

Insights

ZCCHC4-mediated m6A modification on 28S rRNA drives cancer progression. Targeting the ZCCHC4-HPD axis offers a new strategy for treating intrahepatic cholangiocarcinoma (ICC).

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Aberrant N6-methyladenosine (m6A) mRNA modification is linked to cancer progression.
  • The role of m6A modification on ribosomal RNA (rRNA) in cancer remains largely unknown.

Purpose of the Study:

  • To investigate the function of ZCCHC4 and its m6A modification on 28S rRNA in cancer, particularly intrahepatic cholangiocarcinoma (ICC).
  • To elucidate the molecular mechanisms by which ZCCHC4 influences cancer progression and to identify potential therapeutic targets.

Main Methods:

  • Analysis of ZCCHC4 and m6A levels in various cancer types.
  • Functional studies using cell models and in vivo experiments to assess ZCCHC4's role in ICC progression.
  • Mechanistic investigations into ZCCHC4's interaction with the translation initiation complex and mRNA 3' UTR.

Main Results:

  • ZCCHC4 and its m6A modification on 28S rRNA are upregulated in cancers and associated with poor survival.
  • ZCCHC4 promotes ICC progression through its catalytic activity.
  • ZCCHC4 facilitates mRNA circularization and translation by interacting with eIF3G and mRNA 3' UTR.
  • HPD mediates ZCCHC4's effects on tyrosine catabolism and ICC progression.
  • Targeting HPD inhibits ICC progression in vivo.

Conclusions:

  • ZCCHC4-mediated m6A modification on 28S rRNA is a key driver of cancer progression.
  • The ZCCHC4-HPD axis represents a novel molecular mechanism regulating translation and tyrosine catabolism in ICC.
  • Targeting the ZCCHC4-HPD axis holds therapeutic potential for ICC treatment.
Keywords:
28S rRNACP: Molecular biologyZCCHC4carbonylationm6A modificationtyrosine metabolism

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