Cargando…

Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma

CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B...

Descripción completa

Detalles Bibliográficos
Autores principales: Weng, Shao-Wen, Liu, Ting-Ting, Eng, Hock-Liew, You, Huey-Ling, Huang, Wan-Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262180/
https://www.ncbi.nlm.nih.gov/pubmed/34257560
http://dx.doi.org/10.3389/pore.2021.602714
_version_ 1783719139323412480
author Weng, Shao-Wen
Liu, Ting-Ting
Eng, Hock-Liew
You, Huey-Ling
Huang, Wan-Ting
author_facet Weng, Shao-Wen
Liu, Ting-Ting
Eng, Hock-Liew
You, Huey-Ling
Huang, Wan-Ting
author_sort Weng, Shao-Wen
collection PubMed
description CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B expression. Q-score was defined as the sum of the labeling intensity and proportion. The cut-off point for immunoreactivity was set. CUL4A was overexpressed in cell lines and autophagy reflux was compared after manipulation. The iCCA cases with CUL4A overexpression had significantly higher prevalence of intact activated autophagy (42.4 vs. 15.2%; p = 0.003), which was significantly associated with advance tumor stage (34.1% vs. 15.4%; p = 0.032), less extensive necrosis (8.3 vs. 49.3%; p < 0.001), and shortened disease-free survival (mean, 19.6 vs. 65.5 months, p = 0.015). In vitro, iCCA cells with CUL4A overexpression significantly increased LC3II level as compared to the cells under basal condition. Although both cell types showed intact autophagy with increased LC3II expression after bafilomycin A1 treatment, the accumulation of LC3II was higher in CUL4A-overexpressing cells. CUL4A overexpression increased the proliferation of cells as compared with control cells. After treatment with bafilomycin A1, proliferation was inhibited in both cell types, but the effects were more prominent in the cells overexpressing CUL4A. CUL4A promotes autophagy, and exhibits significantly higher autophagic flux which affects the proliferation of iCCA cells; these effects correlated with advance tumor stage and poor prognosis. Thus, targeting autophagy may be potentially therapeutic in iCCA.
format Online
Article
Text
id pubmed-8262180
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82621802021-07-12 Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma Weng, Shao-Wen Liu, Ting-Ting Eng, Hock-Liew You, Huey-Ling Huang, Wan-Ting Pathol Oncol Res Society Journal Archive CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B expression. Q-score was defined as the sum of the labeling intensity and proportion. The cut-off point for immunoreactivity was set. CUL4A was overexpressed in cell lines and autophagy reflux was compared after manipulation. The iCCA cases with CUL4A overexpression had significantly higher prevalence of intact activated autophagy (42.4 vs. 15.2%; p = 0.003), which was significantly associated with advance tumor stage (34.1% vs. 15.4%; p = 0.032), less extensive necrosis (8.3 vs. 49.3%; p < 0.001), and shortened disease-free survival (mean, 19.6 vs. 65.5 months, p = 0.015). In vitro, iCCA cells with CUL4A overexpression significantly increased LC3II level as compared to the cells under basal condition. Although both cell types showed intact autophagy with increased LC3II expression after bafilomycin A1 treatment, the accumulation of LC3II was higher in CUL4A-overexpressing cells. CUL4A overexpression increased the proliferation of cells as compared with control cells. After treatment with bafilomycin A1, proliferation was inhibited in both cell types, but the effects were more prominent in the cells overexpressing CUL4A. CUL4A promotes autophagy, and exhibits significantly higher autophagic flux which affects the proliferation of iCCA cells; these effects correlated with advance tumor stage and poor prognosis. Thus, targeting autophagy may be potentially therapeutic in iCCA. Frontiers Media S.A. 2021-02-23 /pmc/articles/PMC8262180/ /pubmed/34257560 http://dx.doi.org/10.3389/pore.2021.602714 Text en Copyright © 2021 Weng, Liu, Eng, You and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Society Journal Archive
Weng, Shao-Wen
Liu, Ting-Ting
Eng, Hock-Liew
You, Huey-Ling
Huang, Wan-Ting
Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title_full Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title_fullStr Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title_full_unstemmed Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title_short Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma
title_sort autophagy plays a role in the cul4a-related poor prognosis of intrahepatic cholangiocarcinoma
topic Society Journal Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262180/
https://www.ncbi.nlm.nih.gov/pubmed/34257560
http://dx.doi.org/10.3389/pore.2021.602714
work_keys_str_mv AT wengshaowen autophagyplaysaroleinthecul4arelatedpoorprognosisofintrahepaticcholangiocarcinoma
AT liutingting autophagyplaysaroleinthecul4arelatedpoorprognosisofintrahepaticcholangiocarcinoma
AT enghockliew autophagyplaysaroleinthecul4arelatedpoorprognosisofintrahepaticcholangiocarcinoma
AT youhueyling autophagyplaysaroleinthecul4arelatedpoorprognosisofintrahepaticcholangiocarcinoma
AT huangwanting autophagyplaysaroleinthecul4arelatedpoorprognosisofintrahepaticcholangiocarcinoma