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Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway.


ABSTRACT: 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.

SUBMITTER: Cheng L 

PROVIDER: S-EPMC7801402 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m<sup>6</sup>A/p21 pathway.

Cheng Lin L   Zhang Xu X   Huang Yu-Zhou YZ   Zhu Yu-Lan YL   Xu Ling-Yun LY   Li Zhi Z   Dai Xin-Yuan XY   Shi Liang L   Zhou Xu-Jie XJ   Wei Ji-Fu JF   Ding Qiang Q  

Oncogenesis 20210105 1


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 (m<sup>6</sup>A) 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 m<sup>6</sup>A level by m<sup>6</sup>A colorimetric analysis and dot b  ...[more]

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