PAK6通过影响DNA损伤修复促进乳腺癌细胞凋亡OA

Objective To comprehensively analyze the expression,clinical significance,po-tential biological functions,and preliminary mechanisms of PAK6 in breast cancer,and to evaluate its feasibility as a prognostic biomarker and therapeutic target for breast cancer.Methods Breast cancer expression profile data from The Cancer Genome Atlas(TCGA)and Gene Expression Omni-bus(GEO)were utilized to analyze the expression of PAK6 and its relationship with patient prog-nosis.Potential biological functions of PAK6 were explored based on transcriptome data and single-cell RNA sequencing data.The overexpression and knockdown models of PAK6 were established in human breast cancer cell lines MCF7 and MDA-MB-231.JC-1 staining,apoptosis detection,and Western blotting were used to analyze the effects of PAK6 on cell apoptosis and DNA damage re-sponse.Results PAK6 was significantly overexpressed in breast cancer tissues,and its high expres-sion was negatively correlated with overall survival,progression-free survival,disease-specific surviv-al,and relapse-free survival in patients(P<0.05).GSEA results showed that the PAK6 high-expres-sion group was enriched in pathways related to DNA replication,cell cycle regulation,and DNA damage repair.Single-cell analysis revealed that PAK6 was predominantly highly expressed in Malig-nant_C25,Malignant_C28,and Malignant_C3 malignant tumor cell subpopulations.Notably,the Malignant_C25 subpopulation showed enrichment for cell cycle and DNA replication-related pathways and exhibited the potential to transition to other cell types.In vitro experiments confirmed that PAK6 overexpression inhibited apoptosis and decreased the phosphorylation level of the DNA damage mark-er γH2AX in breast cancer cells,whereas PAK6 knockdown promoted apoptosis and increased γH2AX phosphorylation.Conclusion PAK6 is overexpressed in breast cancer and is associated with poor prognosis.It may play a pro-oncogenic role by promoting DNA replication,accelerating cell cycle progression,inhibiting apoptosis,and regulating DNA damage response.PAK6 shows promise as a potential prognostic biomarker and therapeutic target for breast cancer.