USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells

In this study, we discovered that two human oral squamous carcinoma cell (OSCC) lines, SCC9 and SCC25, exhibited varied levels of permissivity to oncolytic HSV-1 T1012G replication and the differential virus yields may associate with the constitutive accumulation of two deubiquitinating enzymes USP1...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ruitao Lu, Guangxian Wu, Meiling Chen, Dongmei Ji, Yonghong Liu, Grace Guoying Zhou, Wenmin Fu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	oncolytic HSV-1 deubiquitinating enzymes USP18 and USP20 STING viral replication Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3aafbc82ac604ea893bee3c686a65e45
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3aafbc82ac604ea893bee3c686a65e45
record_format	dspace
spelling	oai:doaj.org-article:3aafbc82ac604ea893bee3c686a65e452021-11-26T04:35:15ZUSP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells2372-770510.1016/j.omto.2021.11.004https://doaj.org/article/3aafbc82ac604ea893bee3c686a65e452021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001534https://doaj.org/toc/2372-7705In this study, we discovered that two human oral squamous carcinoma cell (OSCC) lines, SCC9 and SCC25, exhibited varied levels of permissivity to oncolytic HSV-1 T1012G replication and the differential virus yields may associate with the constitutive accumulation of two deubiquitinating enzymes USP18 and USP20 in tumor cells. USP18 and USP20 belong to the ubiquitin-specific protease family, mediating the deubiquitination of targets and promoting antiviral responses. Depletion of USP18 or USP20 in SCC9 cells increased T1012G virus yields; overexpression of USP18 or USP20 in SCC25 cells down-regulated T1012G virus replication. In addition, STING as a verified substrate of USP18 and USP20, was found to affect the virus multiplication of T1012G in SCC9 cells. STING knockdown led to an increase in T1012G virus yields in SCC9 cells. Besides, we introduced a deubiquitinating enzyme inhibitor GSK2643943A targeting USP20 and evaluated its effects on viral replication and tumor killing in vitro and in vivo. The results showed that the combination of GSK2643934A and T1012G treatment brought a profound anti-tumor efficacy in mice bearing SCC9 tumors. This report explored factors that play roles in mediating oHSV-1 replication in OSCC tumor cells, facilitating to offer potential targets to improve oHSV-1 oncolytic efficacy and develop candidates of biomarkers to predict the efficiency of oHSV-1 multiplication in tumors.Ruitao LuGuangxian WuMeiling ChenDongmei JiYonghong LiuGrace Guoying ZhouWenmin FuElsevierarticleoncolytic HSV-1deubiquitinating enzymesUSP18 and USP20STINGviral replicationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 477-487 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oncolytic HSV-1 deubiquitinating enzymes USP18 and USP20 STING viral replication Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	oncolytic HSV-1 deubiquitinating enzymes USP18 and USP20 STING viral replication Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ruitao Lu Guangxian Wu Meiling Chen Dongmei Ji Yonghong Liu Grace Guoying Zhou Wenmin Fu USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
description	In this study, we discovered that two human oral squamous carcinoma cell (OSCC) lines, SCC9 and SCC25, exhibited varied levels of permissivity to oncolytic HSV-1 T1012G replication and the differential virus yields may associate with the constitutive accumulation of two deubiquitinating enzymes USP18 and USP20 in tumor cells. USP18 and USP20 belong to the ubiquitin-specific protease family, mediating the deubiquitination of targets and promoting antiviral responses. Depletion of USP18 or USP20 in SCC9 cells increased T1012G virus yields; overexpression of USP18 or USP20 in SCC25 cells down-regulated T1012G virus replication. In addition, STING as a verified substrate of USP18 and USP20, was found to affect the virus multiplication of T1012G in SCC9 cells. STING knockdown led to an increase in T1012G virus yields in SCC9 cells. Besides, we introduced a deubiquitinating enzyme inhibitor GSK2643943A targeting USP20 and evaluated its effects on viral replication and tumor killing in vitro and in vivo. The results showed that the combination of GSK2643934A and T1012G treatment brought a profound anti-tumor efficacy in mice bearing SCC9 tumors. This report explored factors that play roles in mediating oHSV-1 replication in OSCC tumor cells, facilitating to offer potential targets to improve oHSV-1 oncolytic efficacy and develop candidates of biomarkers to predict the efficiency of oHSV-1 multiplication in tumors.
format	article
author	Ruitao Lu Guangxian Wu Meiling Chen Dongmei Ji Yonghong Liu Grace Guoying Zhou Wenmin Fu
author_facet	Ruitao Lu Guangxian Wu Meiling Chen Dongmei Ji Yonghong Liu Grace Guoying Zhou Wenmin Fu
author_sort	Ruitao Lu
title	USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
title_short	USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
title_full	USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
title_fullStr	USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
title_full_unstemmed	USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells
title_sort	usp18 and usp20 restrict ohsv-1 replication in resistant human oral squamous carcinoma cell line scc9 and affect the viability of scc9 cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3aafbc82ac604ea893bee3c686a65e45
work_keys_str_mv	AT ruitaolu usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT guangxianwu usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT meilingchen usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT dongmeiji usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT yonghongliu usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT graceguoyingzhou usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells AT wenminfu usp18andusp20restrictohsv1replicationinresistanthumanoralsquamouscarcinomacelllinescc9andaffecttheviabilityofscc9cells
_version_	1718409836191809536

USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells

Ejemplares similares