As the most predominant RNA epigenetic regulation in eukaryotic cells, N-methyladenosine (mA) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of mA 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 mA target of WTAP. WTAP-mediated mA modification of DIAPH1-AS1 enhanced its stability relying on the mA 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 mA methylation is required for NPC tumorigenesis and metastasis.
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| http://dx.doi.org/10.1038/s41418-021-00905-w | DOI Listing |
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