Integrative Genomic Analysis Identifies MAGT1 as a Key Regulator of Proliferation and Poor Prognosis in Breast Cancer

整合基因组分析发现 MAGT1 是乳腺癌增殖和预后不良的关键调控因子

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Abstract

OBJECTIVE: Magnesium transporter 1 (MAGT1) plays a crucial role in magnesium homeostasis and immune regulation, yet its clinical significance and functional role in breast cancer remain largely unexplored. METHODS: The expression pattern and prognostic value of MAGT1 in breast cancer were analyzed using data from The Cancer Genome Atlas (TCGA) and validated by immunohistochemistry on a tissue microarray comprising 60 patient samples. Genomic alteration analysis of MAGT1 with BRCA clinical implications was performed. The biological functions of MAGT1 were investigated in vitro using MCF-7 and MDA-MB-231 cell lines. MAGT1 expression was knocked down by siRNA, and its effects on cell proliferation, colony formation, DNA synthesis, migration, and invasion abilities were inhibited through MTT assays, colony formation assays, EdU assays, wound healing assays, and Transwell assays. Immune cell infiltration associated with MAGT1 expression was analyzed using bioinformatics tools. RESULTS: MAGT1 was significantly overexpressed in breast cancer tissues compared with adjacent normal tissues. High MAGT1 expression was strongly associated with advanced tumor stage, poorer histological grade, and unfavorable patient prognosis, serving as an independent risk factor for overall survival. MAGT1 mutations were not statistically significantly associated with overall survival (OS) in breast cancer, but MAGT1 mutations were closely associated with ERBB2 and CDH1. Bioinformatic analysis revealed a correlation between MAGT1 expression and altered immune cell infiltration within the tumor microenvironment. In vitro functional assays demonstrated that silencing MAGT1 markedly inhibited the proliferative capacity, clonogenicity, migration, and invasion of breast cancer cells. CONCLUSION: Our findings indicate that MAGT1 is frequently upregulated in breast cancer and correlates with aggressive tumor behavior and poor clinical outcomes. MAGT1 promotes key oncogenic phenotypes in breast cancer cells and may influence the immune landscape, highlighting its potential as both a prognostic biomarker and a promising therapeutic target.

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