PJA2 Suppresses Colorectal Cancer Progression by Controlling HDAC2 Degradation and Stability

• DOI: 10.1002/advs.202401964
• Publication Date: 2025-02-11T05:57:48Z
• Authors: Zhihao Chen; Chaofan Peng; Chi Jin; Ye Wang; Tuo Wang; Peng Yang; Wen Peng; Qingyang Sun; Hengjie Xu; Hongxu Nie; Xiaowei Wang; Junwei Tang; Yueming Sun; Yifei Feng
• Keywords: Chromatin immunoprecipitation; Immunoprecipitation; Histone deacetylase 2

PJA2 is documented to degrade various substrates. Nevertheless, the role of as an E3 ubiquitin-protein ligase in colorectal cancer (CRC) progression remains unexplored. The correlation between mRNA levels and clinical characteristics investigated using data from Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) immunohistochemistry (IHC) are utilized evaluate expression CRC tissues. biological functions confirmed through colony formation assays azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model CRC, among other experimental approaches. underlying molecular mechanisms action elucidated RNA sequencing (RNA-seq), co-immunoprecipitation (co-IP), proximity ligation assay (PLA), chromatin immunoprecipitation (ChIP). Our research discovered that downregulated tissues decreased correlates with poor prognosis. Functionally, vivo vitro experiments uncovered inhibits tumor cell proliferation promotes apoptosis. Mechanistically, recognized histone deacetylase 2 (HDAC2) via its RING-B-box domain (RBD) bind N-terminal HDAC2, facilitating ubiquitination at lysine 90 (K90) residue. PJA2-mediated degradation HDAC2 counteracts transcriptional repression interferon-induced protein tetratricopeptide repeats (IFIT) family, thereby suppressing progression. demonstrates suppresses PJA2/HDAC2/IFIT axis, regulated by thus constituting a positive feedback loop. Consequently, may serve potential therapeutic target for interrupting this loop can represent viable treatment strategy restrain