Epigenetic reactivation of PEG3 by EZH2 inhibitors suppresses renal clear cell carcinoma progress.
Cell Signal
; 107: 110662, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37001595
ABSTRACT
PEG3 is a paternally imprinted gene located on chromosome 19q13.4 and one of the most common low-expression genes in human ovarian cancer. PEG3 plays an important role in p53-related cell death. However, whether PEG3 plays a role in renal clear cell carcinoma (ccRCC) remains unclear. Here, we found that PEG3 was epigenetic inactivated and played a tumor suppressor role in ccRCC. Overexpression of PEG3 inhibited ccRCC cell proliferation and colony formation, while removal of PEG3 significantly promoted cell proliferation in vitro and tumor formation in nude mice in vivo. EZH2-mediated H3K27me3 at the PEG3 promoter suppressed PEG3 expression. EZH2 specific inhibitors promote PEG3 transcriptional expression through the transition from H3K27me3 to H3K27ac at the PEG3 promoter region. Depletion of PEG3 inhibited the activation of the p53 signaling pathway, resulting in the resistance of ccRCC to EZH2 inhibitors treatment. Thus, our data show that EZH2-mediated epigenetic inactivation of PEG3 promotes the progress of ccRCC, and reactivation of PEG3 may be a promising strategy for ccRCC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Renal Cell
/
Kidney Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell Signal
Year:
2023
Document type:
Article
Affiliation country:
China