| Literature DB >> 34999731 |
Zhi-Xuan Li1, Zi-Qi Zheng1, Pan-Yang Yang1, Li Lin1, Guan-Qun Zhou1, Jia-Wei Lv1, Lu-Lu Zhang2, FoPing Chen1, Ying-Qin Li1, Chen-Fei Wu1, Feng Li1, Jun Ma1, Na Liu3, Ying Sun4.
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.Entities:
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Year: 2022 PMID： 34999731 PMCID： PMC9177844 DOI： 10.1038/s41418-021-00905-w
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 12.067