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.

中文翻译：

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METTL14 通过调节 N6-甲基腺苷依赖性初级 miR-375 加工抑制 CRC 进展。

表观遗传改变极大地促进了人类致癌作用。N6-甲基腺苷 (m6A) 是对真核生物中存在的 RNA 分子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) 中的生物学功能仍不清楚。在这里，我们发现 METTL14 在 CRC 组织和细胞系中下调，并与总生存期 (OS) 密切相关。METTL14 敲低显着降低总 RNA 中的 m6A 水平并促进 CRC 细胞生长和转移，而 METTL14 过表达显着增加总 RNA 中的 m6A 水平并抑制 CRC 细胞生长和转移。此外，我们证明了 miR-375 是 METTL14 的下游靶标。我们还证实 METTL14 通过 miR-375/Yes 相关蛋白 1 (YAP1) 途径抑制 CRC 细胞生长，以及通过 miR-375/SP1 通路抑制 CRC 细胞迁移和侵袭。总之，我们的研究显示了 METTL14 在 CRC 进展中的重要作用，并为 m6A 修饰在 CRC 进展中提供了新的见解。