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Cancer Res. 2020 Dec 1;80(23):5174-5188. doi: 10.1158/0008-5472.CAN-19-3626. Epub 2020 Oct 16.
2
WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an mA-dependent manner.WTAP 通过依赖 mA 的方式抑制 HMBOX1 表达促进骨肉瘤肿瘤发生。
Cell Death Dis. 2020 Aug 19;11(8):659. doi: 10.1038/s41419-020-02847-6.
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Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2.相互作用组分析显示，lncRNA HULC 通过 LDHA 和 PKM2 促进有氧糖酵解。
Nat Commun. 2020 Jun 22;11(1):3162. doi: 10.1038/s41467-020-16966-3.
4
Mechanism of RNA modification N6-methyladenosine in human cancer.RNA 修饰 N6-甲基腺苷在人类癌症中的作用机制。
Mol Cancer. 2020 Jun 8;19(1):104. doi: 10.1186/s12943-020-01216-3.
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The potential role of RNA N6-methyladenosine in Cancer progression.RNA N6-甲基腺苷在癌症进展中的潜在作用。
Mol Cancer. 2020 May 12;19(1):88. doi: 10.1186/s12943-020-01204-7.
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mA Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer.mA 修饰在编码和非编码 RNA 中的作用及其在癌症中的治疗意义。
Cancer Cell. 2020 Mar 16;37(3):270-288. doi: 10.1016/j.ccell.2020.02.004.
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mA Methylation of Precursor-miR-320/RUNX2 Controls Osteogenic Potential of Bone Marrow-Derived Mesenchymal Stem Cells.前体微RNA-320/Runx2的甲基化调控骨髓间充质干细胞的成骨潜能
Mol Ther Nucleic Acids. 2020 Mar 6;19:421-436. doi: 10.1016/j.omtn.2019.12.001. Epub 2019 Dec 12.
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IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader.IGF2BP2 通过作为 N6-甲基腺苷的读取器来调节 DANCR。
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WTAP 介导的长链非编码 RNA DIAPH1-AS1 的 mA 修饰增强其稳定性，促进鼻咽癌的生长和转移。

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

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, 510060, Guangzhou, P.R. China.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, 510060, Guangzhou, P.R. China.

出版信息

Cell Death Differ. 2022 Jun;29(6):1137-1151. doi: 10.1038/s41418-021-00905-w. Epub 2022 Jan 8.

DOI:10.1038/s41418-021-00905-w
PMID:34999731
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9177844/
Abstract

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.

摘要

作为真核细胞中最主要的 RNA 表观遗传调控，N6-甲基腺苷（m6A）在人类肿瘤发生和癌症进展中发挥着关键作用。然而，m6A 调控在鼻咽癌（NPC）中的生物学功能和分子机制仍不清楚。在这里，我们发现 Wilms 瘤 1 相关蛋白（WTAP）在 NPC 中明显上调，并且 WTAP 的增加与预后不良有关。NPC 中上调的 WTAP 是由 KAT3A 介导的 H3K27 乙酰化精细调控的。功能上，WTAP 是 NPC 生长和转移所必需的。在机制上，lncRNA DIAPH1-AS1 被鉴定为 WTAP 的一个真正的 m6A 靶标。WTAP 介导的 DIAPH1-AS1 的 m6A 修饰依赖于 mA 阅读器 IGF2BP2 依赖性途径增强了其稳定性。此外，DIAPH1-AS1 作为一种分子衔接物，促进了 MTDH-LASP1 复合物的形成，并上调了 LASP1 的表达，最终促进了 NPC 的生长和转移。因此，WTAP 介导的 DIAPH1-AS1 m6A 甲基化是 NPC 发生和转移所必需的。