CENPF Promotes EMT in Non-small Cell Lung Cancer by Up-regulating ACKR3/CXCR7

Objective To investigate the relationship between the expression of CENPF in NSCLC adenocarcinoma (LUAD) and the clinical prognosis of patients and its effect on the metastasis of lung adenocarcinoma cells.

Methods The expression of CENPF in LUAD and its relationship with patient prognosis were analyzed by online bioinformatics. The expression of CENPF was verified by LUAD tissue microarray immunohistochemical staining. Kaplan-Meier analysis was performed to analyze the relationship between the expression of CENPF and the prognosis of patients with lung adenocarcinoma. Cox survival hazard ratio was used to analyze the factors affecting the survival of patients. Chi-square analysis was adopted to examine the relationship between CENPF expression and clinicopathological stage and grade of patients. The expression of CENPF in NCI-H2126 cells were knocked out by lentivirus, and then the proliferation, invasion, and migration abilities of the cells were detected. Changes in mRNA expression profiles after CENPF knockout were detected by RNA-seq. Bioinformatics analysis of downstream signaling pathways and the target genes of CENPF was also performed. Western blot was used to verify the target gene.

Results CENPF was significantly upregulated in LUAD tumor tissue (P < 0.05) and significantly correlated with pathological stage (P=0.013). The higher expression of CENPF, the worse the prognosis of patients (P=0.01, P=0.027). After the expression was CENPF of knocked out, the cell proliferation, migration, and invasion abilities significantly reduced (P < 0.01). The expression of chemokine pathway genes in cells was enriched significantly (P < 0.001). ACKR3/CXCR7 and CDH2/N-cadherin were significantly downregulated, whereas CDH1/E-cadherin was significantly upregulated. After CENPF was knocked out, ACKR3/CXCR7 and N-cadherin were significantly downregulated, whereas E-cadherin significantly increased.

Conclusion The expression of CENPF is negatively correlated with the clinical prognosis of patients with LUAD, and it promotes the occurrence of EMT by regulating the expression levels of N-cadherin and E-cadherin related to EMT through ACKR3/CXCR7.