CENP-A promotes cervical cancer progression through p53 pathway

Abstract Background: Centromere protein A (CENP-A) is a variant of histone H3 found in the centromeric chromatin, it plays a crucial role in chromosome segregation. The specific mechanisms by which CENP-A regulates cervical cancer (CC) progression have not been previously elucidated. Methods: The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus（GEO）were used to analyze CENP-Aexpression in CC. Gene set enrichment analysis was constructed through GSEA. The expression of CENP-A in CC were tested using immunohistochemistry (IHC) staining. CC cells were transfected with LV- CENP-A-RNAi vector to decrease the CENP-A expression. Cell phenotype assays were used to detect the survival, proliferation and migration of cells. The cell apoptosis of CC cells was analyzed by flow cytometry assays. Result: The expression of CENP-A was higher in cervical cancer tissues and cells compared with that in the adjacent paracancerous tissues. Gene enrichment analysis showed that the genes closely related to CENP-A were mainly related to the cell cycle, oocyte meiosis, pyrimidine metabolism, and the p53 signaling pathway in biological processes. The downregulation of CENP-A resulted in a reduction in the proliferation and migration of CC cells and an increase in cell apoptosis in vitro. In addition, p53, BAX and caspase3 were increased, whereas the expression of Bcl2 was decreased in the CENP-A-downregulated CC cells. After treatment with an antagonist of p53 (Pifithrin-α), the phenotype of CC cells proliferation inhibition was recovered. Conclusion: CENP-A overexpression may be regulated to poor prognosis in patients with cervical cancer. These results suggest that CENP-A may associated with cell apoptosis and proliferation in cervical cancer cells and this may be mediated by p53 signal pathway. CENP-A may be used as a predictor of diagnosis,progression and prognosis in patients with cervical cancer.