Evidence suggests that metformin might be a potential candidate for breast cancer treatment. Yet, its relevant molecular mechanisms remain to be fully investigated. We found that metformin could suppress the N6-methyladenosine (m⁶A) level in breast cancer cells significantly. The latter has an essential role in breast cancer progression and is newly considered as a therapeutic target. In this study, we measured the m⁶A level by m⁶A colorimetric analysis and dot blot assay. We then performed qRT-PCR, western blot, MeRIP, dual-luciferase reporter assay, and others to explore the m⁶A-dependent pathway associated with metformin. In vivo effect of metformin was investigated using a mouse tumorigenicity model. In addition, breast cancer and normal tissues were used to determine the role of METTL3 in breast cancer. Metformin could reduce the m⁶A level via decreasing METTL3 expression mediated by miR-483-3p in breast cancer. METTL3 is known to be able to promote breast cancer cell proliferation by regulating the p21 expression by an m⁶A-dependent manner. Metformin can take p21 as the main target to inhibit such effect. To specify, this study exhibited that metformin can inhibit breast cancer cell proliferation through the pathway miR-483-3p/METTL3/m⁶A/p21. Our findings suggest that METTL3 may be considered as a potential therapeutic target of metformin for breast cancer.

有证据表明二甲双胍可能是乳腺癌治疗的潜在候选者。然而，其相关分子机制仍有待充分研究。我们发现二甲双胍可以显着抑制乳腺癌细胞中的N6-甲基腺苷（m ^{6 A）水平。}后者在乳腺癌进展中发挥重要作用，并被新近视为治疗靶点。在本研究中，我们通过 m ⁶ A 比色分析和斑点印迹测定测量了 m ^{6 A 水平。}然后，我们进行了 qRT-PCR、蛋白质印迹、MeRIP、双荧光素酶报告基因测定等，以探索与二甲双胍相关的m ^{6 A 依赖性途径。}使用小鼠致瘤性模型研究二甲双胍的体内作用。此外，还使用乳腺癌和正常组织来确定METTL3在乳腺癌中的作用。二甲双胍可以通过降低乳腺癌中miR-483-3p介导的METTL3表达来降低m ^{6 A水平。}METTL3已知能够通过m ⁶ A依赖性方式调节p21表达来促进乳腺癌细胞增殖。二甲双胍可以以p21为主要靶点来抑制这种作用。^{具体而言，本研究表明二甲双胍可以通过 miR-483-3p/METTL3/m 6} A/p21途径抑制乳腺癌细胞增殖。我们的研究结果表明 METTL3 可能被认为是二甲双胍治疗乳腺癌的潜在治疗靶点。