Functional and mechanistic study of proto-oncogene SKI mutations in promoting cholangiocarcinoma cells tumorigenesis
10.19405/j.cnki.issn1000–1492.2026.02.008
- VernacularTitle:原癌基因SKI突变促进胆管癌细胞发生的功能和机制研究
- Author:
Dantong ZHA
1
;
Aiqing YANG
2
;
Pengbo CAO
2
;
Xin QI
3
;
Gangqiao ZHOU
1
Author Information
1. School of Life Sciences， Anhui Medical University， Hefei 230032
2. Academy of Military Sciences， Academy of Military Medical Sciences， Beijing 100850
3. Medical College， Guizhou University， Guiyang 550025
- Publication Type:Journal Article
- Keywords:
cholangiocarcinoma;
cholangiocarcinoma cells;
SKI;
cell cycle;
proliferation;
apoptosis;
migration
- From:
Acta Universitatis Medicinalis Anhui
2026;61(2):239-249
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the impact of aberrant SKI expression and its mutations on the biological characteristics of cholangiocarcinoma cell lines QBC939 and RBE， and to explore the underlying molecular mechanisms. MethodsThe Gene Expression Profiling Interactive Analysis 2 （GEPIA2） database was utilized to analyze SKI expression and its clinical relevance in cholangiocarcinoma patients. Lentiviral transduction was employed to establish QBC939 and RBE cell lines with stable SKI overexpression， mutation， or knockdown. Cell proliferation was assessed using CCK-8， colony formation， and EdU assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell migration was evaluated using Transwell and wound healing assays. The effect of SKI over-expression， mutation， or knockdown on key proteins （SMAD2， SMAD3， SMAD4） in the transforming growth factor-β （TGF-β）/Small mothers against decapentaplegic （SMAD） signaling pathway was examined by Western blot. ResultsCompared to SKI overexpression alone， the introduction of SKI mutations significantly promoted S-phase progression， enhanced proliferation and migration， and inhibited apoptosis. Mechanistically， SKI mutations suppressed the phosphorylation of SMAD2 and SMAD3 proteins， thereby inhibiting the transcriptional activity of the TGF-β signaling pathway. Conversely， SKI knockedown produced the opposite effects. ConclusionSKI gene mutation acts as a gain-of-function genetic alteration， exerting an oncogenic role in cholangiocarcinoma cells. The primary mechanism involves the inhibition of the TGF-β/SMAD signaling pathway， which in turn promotes proliferation and cell cycle progression， and suppresses apoptosis in QBC939 and RBE cells， ultimately driving tumor progression.
