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

被引：128

作者：

Li, Zhi-Xuan ^{[1
]}

Zheng, Zi-Qi ^{[1
]}

Yang, Pan-Yang ^{[1
]}

Lin, Li ^{[1
]}

Zhou, Guan-Qun ^{[1
]}

Lv, Jia-Wei ^{[1
]}

Zhang, Lu-Lu ^{[2
]}

Chen, FoPing ^{[1
]}

Li, Ying-Qin ^{[1
]}

Wu, Chen-Fei ^{[1
]}

Li, Feng ^{[1
]}

Ma, Jun ^{[1
]}

Liu, Na ^{[1
]}

Sun, Ying ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China

[2] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Mol Diagnost, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China

来源：

CELL DEATH AND DIFFERENTIATION | 2022年 / 29卷 / 06期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

NONCODING RNAS; METHYLATION; PROGRESSION; EXPRESSION; INSIGHTS; ROLES; CELLS;

D O I：

10.1038/s41418-021-00905-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1137 / 1151

页数：15

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