Cargando…

UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185

Background: Esophageal cancer is the sixth-most common fatal malignant tumor worldwide. Little is known regarding the genetic drivers that influence targeted therapy outcomes in patients with esophageal cancer. Exploring the pathogenesis of this lethal tumor could provide clues for developing approp...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Zhikun, Zhang, Bin, Yu, Haixin, Li, Shoukang, Song, Naicheng, Jin, Xin, Li, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375240/
https://www.ncbi.nlm.nih.gov/pubmed/34421347
http://dx.doi.org/10.7150/ijbs.61117
_version_ 1783740283600502784
author Zheng, Zhikun
Zhang, Bin
Yu, Haixin
Li, Shoukang
Song, Naicheng
Jin, Xin
Li, Jinsong
author_facet Zheng, Zhikun
Zhang, Bin
Yu, Haixin
Li, Shoukang
Song, Naicheng
Jin, Xin
Li, Jinsong
author_sort Zheng, Zhikun
collection PubMed
description Background: Esophageal cancer is the sixth-most common fatal malignant tumor worldwide. Little is known regarding the genetic drivers that influence targeted therapy outcomes in patients with esophageal cancer. Exploring the pathogenesis of this lethal tumor could provide clues for developing appropriate therapeutic drugs. Ubiquitin-protein ligase E3A (UBE3A) reportedly promotes or suppresses various types of malignant tumors. However, the cancer-related role of UBE3A in esophageal cancer remains unclear. Methods: The relationship of UBE3A with the clinicopathological features of pancreatic tumors was bioinformatically investigated in the TCGA dataset. The protein levels of UBE3A and ZNF185 were assessed by Western blot and immunohistochemistry. The role of UBE3A and ZNF185 in esophageal cancer growth was assessed by MTS assays, colony formation assays, and experiments in mouse xenograft models. The interaction between UBE3A and ZNF185 was investigated by co-immunoprecipitation. The relationship between UBE3A, ZNF185, and NOTCH signaling pathway was explored by Western blot and quantitative real-time PCR. Results: We found that UBE3A was upregulated in patients with esophageal cancer and enhanced the cellular progression of esophageal cancer. Moreover, we found that UBE3A degraded ZNF185 in esophageal cancer. Additionally, ZNF185 suppressed the progression of esophageal cancer by inactivating the NOTCH pathway. Conclusions: These data demonstrated that aberrant expression of UBE3A led to enhanced progression of esophageal cancer through the ZNF185/NOTCH signaling axis. Therefore, UBE3A might be an ideal therapeutic candidate for esophageal cancer.
format Online
Article
Text
id pubmed-8375240
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-83752402021-08-19 UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185 Zheng, Zhikun Zhang, Bin Yu, Haixin Li, Shoukang Song, Naicheng Jin, Xin Li, Jinsong Int J Biol Sci Research Paper Background: Esophageal cancer is the sixth-most common fatal malignant tumor worldwide. Little is known regarding the genetic drivers that influence targeted therapy outcomes in patients with esophageal cancer. Exploring the pathogenesis of this lethal tumor could provide clues for developing appropriate therapeutic drugs. Ubiquitin-protein ligase E3A (UBE3A) reportedly promotes or suppresses various types of malignant tumors. However, the cancer-related role of UBE3A in esophageal cancer remains unclear. Methods: The relationship of UBE3A with the clinicopathological features of pancreatic tumors was bioinformatically investigated in the TCGA dataset. The protein levels of UBE3A and ZNF185 were assessed by Western blot and immunohistochemistry. The role of UBE3A and ZNF185 in esophageal cancer growth was assessed by MTS assays, colony formation assays, and experiments in mouse xenograft models. The interaction between UBE3A and ZNF185 was investigated by co-immunoprecipitation. The relationship between UBE3A, ZNF185, and NOTCH signaling pathway was explored by Western blot and quantitative real-time PCR. Results: We found that UBE3A was upregulated in patients with esophageal cancer and enhanced the cellular progression of esophageal cancer. Moreover, we found that UBE3A degraded ZNF185 in esophageal cancer. Additionally, ZNF185 suppressed the progression of esophageal cancer by inactivating the NOTCH pathway. Conclusions: These data demonstrated that aberrant expression of UBE3A led to enhanced progression of esophageal cancer through the ZNF185/NOTCH signaling axis. Therefore, UBE3A might be an ideal therapeutic candidate for esophageal cancer. Ivyspring International Publisher 2021-07-13 /pmc/articles/PMC8375240/ /pubmed/34421347 http://dx.doi.org/10.7150/ijbs.61117 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zheng, Zhikun
Zhang, Bin
Yu, Haixin
Li, Shoukang
Song, Naicheng
Jin, Xin
Li, Jinsong
UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title_full UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title_fullStr UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title_full_unstemmed UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title_short UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185
title_sort ube3a activates the notch pathway and promotes esophageal cancer progression by degradation of znf185
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375240/
https://www.ncbi.nlm.nih.gov/pubmed/34421347
http://dx.doi.org/10.7150/ijbs.61117
work_keys_str_mv AT zhengzhikun ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT zhangbin ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT yuhaixin ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT lishoukang ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT songnaicheng ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT jinxin ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185
AT lijinsong ube3aactivatesthenotchpathwayandpromotesesophagealcancerprogressionbydegradationofznf185