Effect of COL6A3 Regulating the PI3K/AKT Pathway on the Proliferation,Migration,Invasion and Blood-Brain Barrier Penetration Ability of Triple-Negative Breast Cancer Cells
LIANG Zhuming
MO Yanan
ZHANG Yujiao
YU Yanjing
JI Yinan
Abstract：Objective To investigate the effects of VI collagen α3 chain(COL6A3)on the proliferation,migration,invasion and blood-brain barrier penetration ability of triple-negative breast cancer(TNBC)cells through bioinformatics analysis using the cancer genome atlas(TCGA)and the high-throughput gene expression database(GEO).Methods Bioinformatics analysis was conducted using the TCGA and GEO databases to compare the expression of COL6A3 in normal breast tissues,breast cancer(BC)tissues,and BC brain metastases tissues.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were also performed.The expression of COL6A3 in TNBC cells and normal breast cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot(WB).TNBC cells were divided into the transfection negative control group(NC group)and the knockdown group(sh-COL6A3 group)by lentivirus infection,and the transfection status was detected by RT-qPCR and WB.The proliferation,migration,invasion and penetration ability of cells through the blood-brain barrier were detected using the cell counting box-8(CCK-8),cell cloning assay,scratch assay,Transwell assay and in vitro blood-brain barrier model.The correlation between COL6A3 and the PI3K/AKT pathway was verified using WB.Results According to the TCGA data analysis,the expression level of COL6A3 in BC samples was significantly higher than that in normal breast samples(P<0.05),and it was enriched in the PI3K/AKT pathway.Data analysis of GSE125989 showed that the expression level of COL6A3 in BC brain metastatic tumor samples was significantly higher than that in primary BC samples(P<0.05);Compared with normal breast tissue cells,the expression of messenger ribonucleic acid(mRNA)and protein of COL6A3 in TNBC cells was upregulated(P<0.05);Compared with the NC group,the proliferation,migration,invasion and blood-brain barrier penetration ability of TNBC cells in the sh-COL6A3 group were significantly decreased(P<0.05),and the expression of PI3K/AKT pathway marker proteins was down-regulated in the sh-COL6A3 group(P<0.05).Conclusion COL6A3 promotes the proliferation,migration,invasion and penetration of TNBC cells into the blood-brain barrier by regulating the PI3K/AKT pathway.
Keywords：Triple-negative breast cancerVI collagen α3 chainBrain metastasis
Publication Date：2025-05-30
Online Publishing Date：2025-09-15(First online date of this platform, not the publication date of the document)
Pages：7( 1-4,14,后插1-后插2,封3 )