Affiliation:
1. Department of Laboratory Medicine School of Tianjin Medical Technology Tianjin Medical University Tianjin China
2. Department of Human Anatomy School of Basic Medical Sciences Tianjin Medical University Tianjin China
Abstract
AbstractAlthough aberrant methylation of PAX1 is closely associated with cervical cancer (CC), PAX1 methylation (PAX1m) and its role in CC remain to be elucidated. Here, we clarified the biological function of PAX1 in CC. First, PAX1m in ThinPrep cytologic test samples was measured via quantitative methylation‐specific PCR. The results showed that PAX1 promoter methylation levels were significantly increased in CC patients (p < 0.001). We also found that PAX1 promoter methylation levels were positively correlated with tumor purity but negatively correlated with immune‐infiltration via public databases. Then, CRISPR‐based methylation perturbation tools (dCas9‐Tet1) were constructed to further demonstrate that DNA methylation participates in the regulation of PAX1 expression directly. Gain‐ and loss‐of‐function experiments were used to show that PAX1 overexpression restrained proliferation, migration and improved cisplatin sensitivity by interfering with the WNT/TIMELESS axis in CC cells. Additionally, Co‐immunoprecipitation assays further confirmed the interaction between PAX1 and TCF7L2. Taken together, our results suggested that a tumor suppressor role of PAX1 in CC and that CRISPR‐based PAX1 demethylation editing might be a promising therapeutic strategy for CC.