CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression.
CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression.
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CircMETTL3 以 m6A 依赖性方式上调，促进乳腺癌进展
DOI：
10.7150/ijbs.57783
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发表时间：
2021
影响因子：
9.2
通讯作者：
Ding Q
中科院分区：
文献类型：
--
作者：
Li Z;Yang HY;Dai XY;Zhang X;Huang YZ;Shi L;Wei JF;Ding Q
越来越多的证据表明，N6-甲基腺苷(M6A)在肿瘤发生中具有生物学功能。甲基转移酶复合体的催化成分METTL3是甲基转移酶复合体中最重要的部分，在肿瘤发生发展中起着至关重要的作用。然而，从METTL3衍生的CircRNAs在乳腺癌中的生物学功能和潜在的分子机制仍不清楚。在这里，我们报告了大约METTL3，它在乳腺癌中还没有被研究过，但在乳腺癌中显著上调。此外，我们还发现，在乳腺癌中，CircMETTL3可以促进细胞的增殖、迁移和侵袭。机制研究表明，CircMETTL3可能作为miR-31-5p的内源竞争RNA(CerNA)，上调其靶向细胞周期蛋白依赖性激酶(CDK1)的表达。此外，CircMETTL3的m6A修饰可能会影响其表达。综上所述，我们的结果阐明了CircMETTL3通过CircMETTL3/miR-31-5p/CDK1轴促进乳腺癌的进展。此外，CircMETTL3的宿主基因METTL3可能以m6A依赖的方式调节CircMETTL3的表达，而CircMETL3对METTL3的表达没有影响，从而在CircRNA和相应的宿主基因之间提供了一种新的关系。因此，它可能成为乳腺癌治疗的新靶点。
Growing evidence indicates N6-methyladenosine (m6A) has biological function in oncogenesis. METTL3, the catalytic component, is the most important part of methyltransferase complex and plays a crucial role in cancers. However, the biological function of circRNAs derived from METTL3 in breast cancer and the underlying molecular mechanism remains unclear. Herein, we report circMETTL3, which has not been explored in breast cancer, and it is markedly upregulated in breast cancer. Moreover, we uncovered that circMETTL3 could facilitate cell proliferation, migration and invasion in breast cancer. Mechanism investigation showed that circMETTL3 might act as a competing endogenous RNA (ceRNA) of miR-31-5p and upregulate its target cyclin-dependent kinases (CDK1). Moreover, m6A modification of circMETTL3 might affect its expression. Taken together, our results elucidate that circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of circMETTL3, may regulate circMETTL3 expression in an m6A-dependent manner, while circMETTL3 has no effect on METTL3 expression, providing a new relationship between the circRNA and the corresponding host gene. Thus, it may serve as a new therapeutic target for breast cancer.
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