WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis

Cell Death Differ. 2022 Jun;29(6):1137-1151. doi: 10.1038/s41418-021-00905-w. Epub 2022 Jan 8.


As the most predominant RNA epigenetic regulation in eukaryotic cells, N6-methyladenosine (m6A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m6A regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms' tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide m6A target of WTAP. WTAP-mediated m6A modification of DIAPH1-AS1 enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 m6A methylation is required for NPC tumorigenesis and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Adenosine / metabolism
  • Carcinogenesis
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Epigenesis, Genetic
  • Formins* / genetics
  • Formins* / metabolism
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / metabolism
  • Nasopharyngeal Carcinoma* / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • Neoplasm Metastasis
  • RNA Splicing Factors* / genetics
  • RNA Splicing Factors* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Formins
  • IGF2BP2 protein, human
  • LASP1 protein, human
  • LIM Domain Proteins
  • MTDH protein, human
  • Membrane Proteins
  • RNA Splicing Factors
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • WTAP protein, human
  • N-methyladenosine
  • Adenosine