METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing (Retracted article. See vol. 30, pg. 2640, 2022)
METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing (Retracted article. See vol. 30, pg. 2640, 2022)
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DOI：
10.1016/j.ymthe.2019.11.016
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发表时间：
2020-02-05
影响因子：
12.4
通讯作者：
Wang, Shukui
中科院分区：
文献类型：
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作者：
Chen, Xiaoxiang;Xu, Mu;Wang, Shukui
表观遗传改变在很大程度上促进了人类的癌症发生。N6-甲基腺苷(M6A)是真核生物中对RNA分子进行的最具预防性和最丰富的修饰之一。然而，M6A甲基化在结直肠癌(CRC)中的生物学功能仍很不清楚。在这里，我们发现METTL14在大肠癌组织和细胞系中表达下调，并与总生存期(OS)密切相关。METTL14基因敲除可显著降低结直肠癌细胞总RNA中m6A的水平，促进结直肠癌细胞的生长和转移，而过表达METTL14则显著增加总RNA中的m6A水平，抑制结直肠癌细胞的生长和转移。此外，我们还证明miR-375是METTL14的下游靶点。我们还证实了METTL14通过miR-375/Yes相关蛋白1(YAP1)途径抑制结直肠癌细胞生长，并通过miR-375/SP1途径抑制结直肠癌细胞的迁移和侵袭。综上所述，我们的研究显示了METTL14在结直肠癌进展中的重要作用，并为M6A修饰在结直肠癌进展中的作用提供了新的见解。
Epigenetic alterations contributed to human carcinogenesis immensely. N6-methyladenosine (m6A) is one of the most preventive and abundant modifications on RNA molecules present in eukaryotes. However, the biological function of m6A methylation in colorectal cancer (CRC) remains largely unclear. Here, we found that METTL14 was downregulated in CRC tissues and cell lines, and closely correlated with overall survival (OS). METTL14 knockdown significantly reduced m6A levels in total RNAs and promoted CRC cell growth and metastasis, whereas METTL14 overexpression markedly increased m6A levels in total RNA and inhibited CRC cell growth and metastasis. Furthermore, we demonstrated that miR-375 was a downstream target of METTL14. We also verified that METTL14 suppressed CRC cell growth via the miR-375/Yes-associated protein 1 (YAP1) pathway, as well as inhibited CRC cell migration and invasion through the miR-375/SP1 pathway. Taken together, our studies showed an important role for METTL14 in CRC progression and provided novel insight into m6A modification in CRC progression.