DataSheet_1_METTL3 Is Suppressed by Circular RNA circMETTL3/miR-34c-3p Signaling and Limits the Tumor Growth and Metastasis in Triple Negative Breast Cancer.docx

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC.

尽管N6-甲基腺嘌呤（N6-methyladenosine, m6A）在诸多生物学过程中具有关键功能，但目前关于其在三阴性乳腺癌（Triple-Negative Breast Cancer, TNBC）潜在调控机制中的研究仍较为匮乏。本研究针对m6A甲基化RNA水平及其核心甲基转移酶METTL3在三阴性乳腺癌进展中的病理作用与潜在调控机制展开探究。研究结果显示，三阴性乳腺癌组织与细胞系中的m6A甲基化RNA水平显著下调。功能实验证实，METTL3可抑制三阴性乳腺癌细胞的增殖、迁移与侵袭能力。此外，本研究发现三阴性乳腺癌细胞中miR-34c-3p可对METTL3的表达产生抑制作用。机制研究表明，circMETTL3可作为miR-34c-3p的分子海绵，通过上调miR-34c-3p靶基因METTL3的表达，进而抑制细胞增殖、侵袭、肿瘤生长及转移。综上，本研究阐明了METTL3在抑制三阴性乳腺癌生长过程中的功能重要性及其调控机制。