γ-Synuclein protects colon cancer cells through autophagy regulation
10.3969/j.issn.1000-4718.2024.00.022
- VernacularTitle:γ-突触核蛋白通过调控自噬对结肠癌细胞起保护作用
- Author:
Qing YE
1
,
2
;
Jinhu CHEN
;
Shengyuan LIU
;
Yangming LI
;
Lijie HUANG
;
Yangmei XU
;
Feng HUANG
Author Information
1. 福建医科大学肿瘤临床医学院,福建省肿瘤医院大肠外科,福建 福州 350014
2. 福建省肿瘤生物治疗重点实验室,福建 福州 350014
- Keywords:
γ-synuclein;
colon cancer;
endoplasmic reticulum stress;
autophagy;
apoptosis
- From:
Chinese Journal of Pathophysiology
2024;40(9):1612-1621
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effects of γ-synuclein on autophagy and apoptosis of colon cancer cells in-duced by endoplasmic reticulum stress,as well as the protective effect on the cells.METHODS:Gene expression profile chip analysis was performed to compare the cDNA expression profiles between human colon cancer HCT116 cells with γ-synu-clein knockdown and HCT116 cells with control siRNA,and to identify potential molecules related to autophagy and apop-tosis.In colon cancer cell lines,the functional effects of γ-synuclein on autophagy and apoptosis induced by thapsigargin(TG),an endoplasmic reticulum stress-inducing agent,were systematically explored by conducting immunofluorescence staining,Western blot,CCK-8 assay,flow cytometry,and transmission electron microscopy.Western blot was used to de-tect the expression of γ-synuclein protein,autophagy-related proteins[microtubule-associated protein 1 light chain 3(LC3),beclin-1,autophagy-related protein 5(ATG5)and ATG7],and apoptosis-related proteins[poly(ADP-ribose)polymerase(PARP),pro-caspase-3,and pro-caspase-9].To further analyze the mechanism of γ-synuclein in regulating autophagy and apoptosis,extracellular signal-regulated kinase(ERK)inhibitor PD98059,ERK inhibitor SP600125 and c-Jun N-terminal kinase(JNK)activator anisomycin were applied separately to test HCT116 cells transfected with γ-synu-clein siRNA.Subsequently,autophagy proteins,apoptosis proteins,and ERK and JNK pathway-related proteins were de-tected by Western blot.RESULTS:The TG-induced autophagy of colon cancer cells mainly occurred at the early stage(0～24 h),and apoptosis mainly occurred at the late stage(36～48 h).Endoplasmic reticulum stress up-regulated the ex-pression of γ-synuclein in colon cancer cells,which was associated with enhanced autophagy.γ-Synuclein promoted au-tophagy by activating ERK and JNK pathways at the early stage(0～24 h),and inhibited apoptosis by blocking JNK path-ways at the late stage(24～48 h)to protect HCT116 cells.In our model,γ-synuclein was observed to play a critical role in the transition from endoplasmic reticulum stress-induced autophagy to apoptosis.CONCLUSION:In the context of endo-plasmic reticulum stress,γ-synuclein promotes autophagy and inhibits apoptosis by regulating ERK and JNK signaling pathways,thus protecting colon cancer cells.This provides a potential idea for anti-tumor therapy.
