Ruan Han-Guang, Gu Wen-Chao, Xia Wen, Gong Yan, Zhou Xue-Liang, Chen Wen-Yan, Xiong Juan
Department of Breast Oncology, The Third Hospital of Nanchang, Nanchang, China.
Department of Diagnostic of Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
Front Oncol. 2021 Dec 22;11:778132. doi: 10.3389/fonc.2021.778132. eCollection 2021.
Despite N6-methyladenosine (mA) 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 mA methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the mA 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（mA）在各种生物学过程中具有重要功能，但其在三阴性乳腺癌（TNBC）潜在调控机制中的作用仍不清楚。在本研究中，我们探究了mA甲基化RNA水平及其主要甲基转移酶METTL3在TNBC进展中的病理作用及潜在机制。我们发现，TNBC组织和细胞系中mA甲基化RNA显著降低。在功能上，我们证明METTL3抑制TNBC细胞的增殖、迁移和侵袭能力。此外，我们发现TNBC细胞中METTL3受miR-34c-3p抑制。在机制方面，我们发现环状METTL3（circMETTL3）可作为miR-34c-3p的海绵，通过上调miR-34c-3p靶基因METTL3的表达来抑制细胞增殖、侵袭、肿瘤生长和转移。总之，我们的研究证明了METTL3在抑制TNBC肿瘤生长中的功能重要性及调控机制。
