MATR3 promotes proliferation and invasion of colon adenocarcinoma cells: bulk, single-cell transcriptomic analysis and experimental validation

BACKGROUND: MATR3 is a DNA/RNA binding nuclear matrix protein involved in RNA processing, transcriptional regulation, and DNA damage response. However, its role in colon adenocarcinoma (COAD) is still unclear. METHODS: Integrating transcriptomic data from TCGA-COAD and single-cell RNA sequencing data from GSE139555, evaluate the expression of MATR3 and its distribution in the tumor microenvironment. GeneMANIA, GO, KEGG, and GSEA analyses were used to explore the biological functions and pathways related to MATR3. The CIBERSORT and pRRophetic software packages are used to evaluate immune infiltration and drug sensitivity. The biological effects of MATR3 knockout were validated using qRT PCR, Western blotting, CCK-8, Transwell assays, and animal models. RESULTS: Compared with normal tissues, the expression of MATR3 was significantly upregulated in COAD tissues. Single cell analysis showed heterogeneity in the expression of MATR3 in tumor microenvironment cell populations, with relatively high expression in CD8+T cell subsets. Functional enrichment analysis showed that MATR3 related genes are mainly involved in RNA splicing, apoptosis related processes, mRNA monitoring, spliceosome pathways, and cell cycle regulation. The expression of MATR3 is associated with multiple immune cell populations and predicted drug responses. In vitro, MATR3 knockout inhibits the proliferation, migration, and invasion of HCT116 and Lovo cells. In vivo, the decrease in MATR3 expression inhibits tumor growth. CONCLUSION: MATR3 is upregulated in COAD, which may promote tumor progression by regulating cell proliferation, invasion, cell cycle related pathways, and immune microenvironment. This study provides new insights into precision oncology.