Reactivation of methylation-silenced PAX1 inhibits cervical cancer proliferation and migration via the WNT/TIMELESS pathway.
Mol Carcinog
; 63(7): 1349-1361, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38712797
ABSTRACT
Although 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
Uterine Cervical Neoplasms
/
DNA Methylation
/
Cell Proliferation
/
Wnt Signaling Pathway
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
China