Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4

Abstract Background Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find...

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Autores principales:	Honghu Xie, Yu He, Yugang Wu, Qicheng Lu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	UBE2D1 SMAD4 EMT GC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/5d5007ca026846e5bb4d44006a7cc1f8
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spelling	oai:doaj.org-article:5d5007ca026846e5bb4d44006a7cc1f82021-11-14T12:13:21ZSilencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD410.1186/s13027-021-00402-21750-9378https://doaj.org/article/5d5007ca026846e5bb4d44006a7cc1f82021-11-01T00:00:00Zhttps://doi.org/10.1186/s13027-021-00402-2https://doaj.org/toc/1750-9378Abstract Background Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC. Methods In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples. Results Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4. Conclusion Silencing of UBE2D1 inhibited cell migration through transforming growth factor β (TGF-β)/SMAD4 signaling pathway in GC.Honghu XieYu HeYugang WuQicheng LuBMCarticleUBE2D1SMAD4EMTGCNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282Infectious and parasitic diseasesRC109-216ENInfectious Agents and Cancer, Vol 16, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	UBE2D1 SMAD4 EMT GC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Infectious and parasitic diseases RC109-216
spellingShingle	UBE2D1 SMAD4 EMT GC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Infectious and parasitic diseases RC109-216 Honghu Xie Yu He Yugang Wu Qicheng Lu Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
description	Abstract Background Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC. Methods In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples. Results Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4. Conclusion Silencing of UBE2D1 inhibited cell migration through transforming growth factor β (TGF-β)/SMAD4 signaling pathway in GC.
format	article
author	Honghu Xie Yu He Yugang Wu Qicheng Lu
author_facet	Honghu Xie Yu He Yugang Wu Qicheng Lu
author_sort	Honghu Xie
title	Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
title_short	Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
title_full	Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
title_fullStr	Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
title_full_unstemmed	Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4
title_sort	silencing of ube2d1 inhibited cell migration in gastric cancer, decreasing ubiquitination of smad4
publisher	BMC
publishDate	2021
url	https://doaj.org/article/5d5007ca026846e5bb4d44006a7cc1f8
work_keys_str_mv	AT honghuxie silencingofube2d1inhibitedcellmigrationingastriccancerdecreasingubiquitinationofsmad4 AT yuhe silencingofube2d1inhibitedcellmigrationingastriccancerdecreasingubiquitinationofsmad4 AT yugangwu silencingofube2d1inhibitedcellmigrationingastriccancerdecreasingubiquitinationofsmad4 AT qichenglu silencingofube2d1inhibitedcellmigrationingastriccancerdecreasingubiquitinationofsmad4
_version_	1718429347782590464

Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4

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