Astragalus Polysaccharide Attenuates Breast Cancer Progression by Regulating METTL3-Mediated MAL2 m⁶A Modification

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Astragalus polysaccharide (APS) shows antitumor potential, but its mechanism in breast cancer (BC) is unclear.
• N6-methyladenosine (m⁶A) modification plays a role in cancer development.
• Understanding APS's regulatory mechanism in BC pathogenesis is crucial for therapeutic development.

Purpose of the Study:

• To investigate the regulatory mechanism of APS in breast cancer (BC) pathogenesis.
• To examine APS's influence on the N6-methyladenosine (m⁶A) modification of MAL2 in BC.
• To assess MAL2 as a potential therapeutic target for enhancing APS efficacy.

Main Methods:

• Cell proliferation, migration, and invasion assays (CCK8, EdU, transwell) were used to evaluate APS effects.
• Tumor xenograft models assessed in vivo tumor growth inhibition.
• Bioinformatics analysis, qRT-PCR, MeRIP, and western blotting were employed to study MAL2 expression and m⁶A modification mediated by METTL3.

Main Results:

• APS significantly reduced proliferation, migration, and invasion in BC cell lines (MCF-7, MDA-MB-231) and suppressed tumor growth in vivo.
• APS treatment led to downregulation of MAL2 expression in BC cells.
• METTL3-mediated m⁶A modification of MAL2 was identified as a key regulatory mechanism in BC tumorigenesis, and MAL2 overexpression partially reversed APS's anti-tumor effects.

Conclusions:

• APS exerts anti-tumor effects in breast cancer by reducing METTL3 expression and altering MAL2 m⁶A modification, thereby inhibiting BC progression.
• MAL2 is significantly downregulated by APS and plays a role in BC malignancy.
• MAL2 represents a potential therapeutic target for improving the efficacy of APS in breast cancer treatment.