Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Int J Mol Sci. 2021 May 21;22(11):5432. doi: 10.3390/ijms22115432.
The association of RNA modification in cancer has recently been highlighted. Methyltransferase like 8 (METTL8) is an enzyme and its role in mRNA m3C modification has barely been studied. In this study, we found that METTL8 expression was significantly up-regulated in canine mammary tumor and investigated its functional roles in the tumor process, including cancer cell proliferation and migration. METTL8 expression was up-regulated in most human breast cancer cell lines tested and decreased by Yin Yang 1 (YY1) transcription factor knockdown, suggesting that YY1 is a regulating transcription factor. The knockdown of METTL8 attenuated tumor cell growth and strongly blocked tumor cell migration. AT-rich interactive domain-containing protein 1A (ARID1A) was identified as a candidate mRNA by METTL8. ARID1A mRNA binds to METTL8 protein. ARID1A mRNA expression was not changed by METTL8 knockdown, but ARID1A protein level was significantly increased. Collectively, our study indicates that METTL8 up-regulated by YY1 in breast cancer plays an important role in cancer cell migration through the mRNA modification of ARID1A, resulting in the attenuation of its translation.
RNA 修饰在癌症中的相关性最近受到了关注。甲基转移酶样 8（METTL8）是一种酶，其在 mRNA m3C 修饰中的作用几乎没有被研究过。在这项研究中，我们发现 METTL8 在犬乳腺肿瘤中表达明显上调，并研究了其在肿瘤过程中的功能作用，包括癌细胞增殖和迁移。METTL8 的表达在大多数测试的人乳腺癌细胞系中上调，并通过 Yin Yang 1（YY1）转录因子敲低而降低，表明 YY1 是一种调节转录因子。METTL8 的敲低减弱了肿瘤细胞的生长并强烈阻止了肿瘤细胞的迁移。富含 AT 的相互作用结构域蛋白 1A（ARID1A）被鉴定为 METTL8 的候选 mRNA。ARID1A mRNA 与 METTL8 蛋白结合。METTL8 敲低后 ARID1A mRNA 表达没有变化，但 ARID1A 蛋白水平显著增加。总的来说，我们的研究表明，在乳腺癌中由 YY1 上调的 METTL8 通过 ARID1A 的 mRNA 修饰在癌细胞迁移中发挥重要作用，导致其翻译减弱。
