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

## TL;DR

Astragalus polysaccharide slows breast cancer growth by altering MAL2 gene modification through METTL3, offering a potential new treatment target.

## Contribution

APS's novel mechanism of action via METTL3-mediated m6A modification of MAL2 in breast cancer is identified.

## Key findings

- APS reduced cell proliferation, migration, and invasion in MCF-7 and MDA-MB-231 cell lines.
- APS suppressed tumor growth in vivo and downregulated MAL2 expression in breast cancer cells.
- Overexpression of MAL2 reversed APS's anti-tumor effects, highlighting its regulatory role.

## Abstract

Astragalus polysaccharide (APS) has recently emerged as a potent antitumor agent, however its impact on breast cancer (BC) remains inadequately understood. The current research aimed to examine the regulatory mechanism of APS in the pathogenesis of BC examining its influence on N6-methyladenosine (m6A) modification of MAL2. The effect of APS on the malignant phenotypes of BC was assessed by CCK8, EdU, transwell and tumor xenograft model assays. The differentially expressed genes (DEGs) in BC were identified by GEPIA-BC database, and their expression levels were determined by qRT-PCR in the BC cells. The role of MAL2 in BC malignancy was examined by EdU and transwell assays. Furthermore, bioinformatics analysis was first employed to explore the m6A modification site of MAL2 mediated by METTL3, which was then validated through MeRIP, western blotting, and qRT-PCR assays. APS was found to significantly reduce the cell proliferation, migration, as well as invasion of MCF-7 (IC50: 1014 μg/ml) and MDA-MB-231 (IC50: 685 μg/ml) cell lines. Additionally, it effectively suppressed tumor growth in vivo. The bioinformatics analysis revealed that among the five DEGs, MAL2 was significantly downregulated upon APS treatment both BC cell lines. Furthermore, the overexpression of MAL2 partially reversed the anti-tumor effects of APS. Notably, METTL3 modulates the m6A modification of MAL2 to regulate tumorigenesis in BC. APS prevents BC progression in association with reduced METTL3 expression and altered m6A modification of MAL2, suggesting that MAL2 may represent a potential therapeutic target to enhance the efficacy of APS.