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

Abstract

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.

• Authors: Zhi-Xuan Li, Zi-Qi Zheng, Pan-Yang Yang, Li Lin, Guan-Qun Zhou, Jia-Wei Lv, Lu-Lu Zhang, FoPing Chen, Ying-Qin Li, Chen-Fei Wu, Feng Li, Jun Ma, Na Liu, Ying Sun
• Journal: Cell death and differentiation (Cell Death Differ) Vol. 29 Issue 6 Pg. 1137-1151 (06 2022) ISSN: 1476-5403 [Electronic] England
• PMID: 34999731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.

Chemical References

• 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

Topics

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