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WTAP-mediated m(6)A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis
- Source :
- Cell Death Differ
- Publication Year :
- 2022
- Publisher :
- Nature Publishing Group UK, 2022.
-
Abstract
- As the most predominant RNA epigenetic regulation in eukaryotic cells, N(6)-methyladenosine (m(6)A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m(6)A 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 m(6)A target of WTAP. WTAP-mediated m(6)A modification of DIAPH1-AS1 enhanced its stability relying on the m(6)A 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 m(6)A methylation is required for NPC tumorigenesis and metastasis.
- Subjects :
- Adenosine
Nasopharyngeal Carcinoma
Carcinogenesis
Formins
Membrane Proteins
RNA-Binding Proteins
Cell Cycle Proteins
Nasopharyngeal Neoplasms
Cell Biology
LIM Domain Proteins
Article
Epigenesis, Genetic
Cytoskeletal Proteins
Cell Line, Tumor
Humans
RNA, Long Noncoding
RNA Splicing Factors
Neoplasm Metastasis
Molecular Biology
Adaptor Proteins, Signal Transducing
Cell Proliferation
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Death Differ
- Accession number :
- edsair.doi.dedup.....9390a06f08778c0155b5121bd4437863