| RRC ID |
87234
|
| Author |
Chen CP, Hung TH, Huang Y, Pan YR, Yeh CN, Huang WK, Hsiao YT, Lo CH, Yu AL, Yu J, Wu CE.
|
| Title |
PufA drives cholangiocarcinoma progression via NFκB signaling activation: a novel therapeutic target.
|
| Journal |
Cancer Gene Ther
|
| Abstract |
Cholangiocarcinoma (CCA) exhibits poor prognosis despite recent advances in targeted therapy and immunotherapy. Therefore, uncovering novel mechanisms of CCA tumorigenesis and identifying effective targeted therapies are critical for improving treatment outcomes in advanced cases. PufA, a newly identified member of the Puf-family RNA-binding proteins and a biogenesis factor, is overexpressed in CCA and correlates with poor survival outcomes. Functional studies demonstrate that PufA silencing in CCA cell lines significantly reduces cell viability, induces apoptosis, and suppresses migration by inhibiting epithelial-mesenchymal transition (EMT). Additionally, PufA knockdown impairs sphere formation in vitro and inhibits tumor growth in xenograft mouse models. RNA sequencing analysis reveals significant downregulation of RELA encodes protein of p65, which encodes the p65 protein, a critical subunit for NFκB signaling activation, suggesting a connection between PufA and the NFκB signaling pathway. Mechanistic investigations confirm that PufA promotes IκBα degradation, thereby activating the NFκB signaling and regulating downstream cytokine expression, including IL1A. Conversely, PufA overexpression enhances IκBα degradation following TNFα stimulation in CCA cells, supporting the correlation between PufA and the NFκB signaling pathway. These findings establish PufA as a pivotal regulator of CCA progression and highlight the PufA-NFκB axis as a potential therapeutic target. This study provides critical insights into the molecular drivers of CCA and lays a foundation for developing novel treatments to enhance patient outcomes.
|
| Volume |
33(1)
|
| Pages |
132-144
|
| Published |
2026-1-1
|
| DOI |
10.1038/s41417-025-00968-8
|
| PII |
10.1038/s41417-025-00968-8
|
| PMID |
41275006
|
| MeSH |
Animals
Bile Duct Neoplasms* / genetics
Bile Duct Neoplasms* / metabolism
Bile Duct Neoplasms* / pathology
Cell Line, Tumor
Cholangiocarcinoma* / genetics
Cholangiocarcinoma* / metabolism
Cholangiocarcinoma* / pathology
Disease Progression
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Humans
Mice
NF-kappa B* / metabolism
Signal Transduction
Xenograft Model Antitumor Assays
|
| IF |
4.534
|
| Resource |
| Human and Animal Cells |
RBE(RCB1292)
SSP-25(RCB1293)
TFK-1(RCB2537) |
