YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation
YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation
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YTH 结构域家族 2 通过促进 6-磷酸葡萄糖酸脱氢酶 mRNA 翻译来促进肺癌细胞生长。
DOI：
10.1093/carcin/bgz152
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发表时间：
2020-05-01
期刊：
影响因子：
4.7
通讯作者：
Shan, Changliang
中科院分区：
文献类型：
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作者：
Sheng, Hao;Li, Zhen;Shan, Changliang
N6-甲基腺苷 (m6A) 是真核生物中广泛存在的转录后 mRNA 修饰之一，m6A 修饰在多种人类癌症中发挥着关键作用。然而，m6A 结合蛋白在癌症代谢中的作用仍然难以捉摸。在这里，我们报告 YTH 结构域家族 2 (YTHDF2) 在肺癌组织中上调，促进肺癌细胞生长并增强磷酸戊糖途径 (PPP) 通量，这对肿瘤生长至关重要。从机制上讲，YTHDF2直接结合6-磷酸葡萄糖酸脱氢酶（6PGD）三素非翻译区（3'-UTR）的m6A修饰位点，促进肺癌细胞中6PGD mRNA的翻译。总的来说，我们的数据表明 YTHDF2 作为肿瘤启动子，通过促进 6PGD mRNA 翻译来增强肿瘤生长。
N6-methyladenosine (m6A) is one of widespread post-transcriptional mRNA modifications in eukaryotes and the m6A modification plays critical roles in various human cancers. However, the role of m6A-binding proteins in cancer metabolism remains elusive. Here, we report that YTH domain family 2 (YTHDF2) is upregulated in lung cancer tissues, promotes lung cancer cell growth and enhances the pentose phosphate pathway (PPP) flux, which is crucial for tumor growth. Mechanistically, YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase (6PGD) three prime untranslated region (3′-UTR) to promote 6PGD mRNA translation in lung cancer cells. Collectively, our data indicate that YTHDF2 acts as a tumor promoter to enhance tumor growth via facilitating 6PGD mRNA translation.