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Archive > Volume 31 Issue 5 > 2024,31(5):462-468. DOI:10.3872/j.issn.1007-385X.2024.05.005 Prev Next
Basic Research
The role of KRT6A in regulating the biological behavior of pancreatic ductal adenocarcinoma PANC1 cells and its role as a target for diagnosis and prognosis
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Abstract:
Objective: To study, through bioinformatics analysis and cellular biology experiments, the effects of keratin 6A (KRT6A)on the diagnosis, prognosis and immune microenvironment of pancreatic ductal adenocarcinoma (PDAC) and biological behaviors of PDAC PANC1 cells, such as proliferation and apoptosis. Methods: The GEPIA platform was used to integrate the data from the TCGA (The Cancer Genome Atlas) and the GTEx (Genotype-Tissue) to analyze the KTRT6A expression in PDCA tissues. CIBERSORT software was then used to analyze the correlation between KRT6A expression and immune cell infiltration in PDCA tissues, and GSEA analysis was used to study the signaling pathway related to KRT6A gene expression. Immunohistochemical analysis was performed on cancer and adjacent tissue samples from 60 PDAC patients preserved in the Department of Pathology of Changhai Hospital to verify the expression of KRT6A in tumor tissues. The expression of KRT6A gene in PANC1 cells was inhibited by interfering with siRNA. The effects of KRT6A on the proliferation and apoptosis of PDAC cells were detected by CCK-8 assay and flow cytometry. Results: Data analysis of the TCGA and the GTEx found that KRT6A was highly expressed in human PDAC tissues and was significantly correlated with poor survival period of patients (P=0.015). CIBERSORT software and GSEA analysis showed that the infiltration of M2-type macrophages in PDCA tissues with high KRT6A expression was increased (P=0.034), and there was a significant correlation between high KRT6A expression and the up-regulation of Wnt pathway (NES: 1.7359272, P<0.05), pentose phosphate pathway (PPP) (NES:1.5613053, P<0.05) and other signaling pathways (P<0.05 or P<0.01). Immunohistochemical results further verified the high expression of KRT6A in PDCA tissues (P<0.001). Proliferation and apoptosis experiments showed that interfering with KRT6A gene could significantly inhibit the proliferation (P<0.05) and apoptosis (P<0.001) of PANC1 cells. Conclusion: KRT6A is highly expressed in human PDAC tissues, and knocking down its expression can inhibit the proliferation and apoptosis of PANC1 cells, and has the potential to be a new target for PDAC diagnosis and prognosis.
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