Work

Expression patterns of Slc38a4 and mmu-miR-6948-3p in a murine model of metastatic triple-negative breast cancer

Year: 2026

Type: article

Abstract: SLC38A4 (SNAT4), a system A amino acid transporter, contributes to nutrient uptake and metabolic regulation, but its role in the progression of triple-negative breast cancer (TNBC) is unclear. We examined the expression of Slc38a4 and its predicted regulatory miRNA, mmu-miR-6948-3p , in primary tumors, invasive mammary tumors, and lung metastases in a murine TNBC model. RNA-sequencing data (GSE150928) from primary mammary tumors and lung metastases were analyzed to identify differentially expressed genes (DEGs), followed by functional enrichment, protein–protein interaction (PPI) network analysis, and miRNA–mRNA target prediction. Eighteen female BALB/c mice implanted with 4T1 TNBC cells were grouped into those with primary mammary tumors and those with lung metastases. Expression of Slc38a4 and mmu-miR-6948-3p was measured by quantitative real-time PCR (qRT–PCR). Public human datasets (TCGA, MET500, DepMap) were also examined. In the RNA-seq data, Slc38a4 was upregulated in lung metastases relative to primary tumors (logFC = 3.93) and was assigned to a PPI cluster enriched for amino acid transport and vesicle trafficking. qRT–PCR confirmed higher Slc38a4 expression in lung metastases (6.23 ± 0.48 vs. 1.00 ± 0.08, P < 0.0001) and lower expression in invasive mammary tumors (0.51 ± 0.05 vs. 1.00 ± 0.08, P < 0.0001) than in primary tumors. Levels of mmu-miR-6948-3p did not differ significantly between groups. In human data, SLC38A4 mRNA was lower in breast tumors than in normal breast tissue, and DNA methylation showed no clear relationship with its expression. Slc38a4 expression depends on tissue context during TNBC progression, being lower in invasive mammary tumors and higher in lung metastases, and this pattern is not explained by changes in mmu-miR-6948-3p. Functional studies are needed to determine whether the increase in the lung drives colonization or is an adaptive response to it.

Source: Scientific Reports

DOI: 10.1038/s41598-026-76356-5

Authors: Parisa Farzamfar, Zivar Salehi, Farhad Mashayekhi, Siamak Khodayari

Institution: University of Guilan

Language: English

Topic: Amino Acid Enzymes and Metabolism

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690