Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma

Neddylation is a process in which a ubiquitin-like molecule NEDD8 is conjugated to a lysine residue of the substrate protein via successive enzymatic cascade reactions. Inactivation of neddylation pathway triggers tumor cell apoptosis or senescence to suppress the tumor growth. So far, there has bee...

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Autores principales:	Lisha Zhou, Luyi Zhang, Siyuan Chen, Dongsheng Sun, Jianhua Qu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	neddylation Th2 cells STAT5A hepatocellular carcinoma immune response Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0af8430a758a4f4d948056a9211b00fb
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spelling	oai:doaj.org-article:0af8430a758a4f4d948056a9211b00fb2021-11-05T09:35:09ZElevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma2234-943X10.3389/fonc.2021.709170https://doaj.org/article/0af8430a758a4f4d948056a9211b00fb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.709170/fullhttps://doaj.org/toc/2234-943XNeddylation is a process in which a ubiquitin-like molecule NEDD8 is conjugated to a lysine residue of the substrate protein via successive enzymatic cascade reactions. Inactivation of neddylation pathway triggers tumor cell apoptosis or senescence to suppress the tumor growth. So far, there has been limited research on the role of the neddylation pathway (NEDD8-UBE2M-RBX1 axis) in the immune response. In this study, we investigated the association between the neddylation pathway and immune function in HCC by comprehensively analyzing transcriptome and clinical data of HCC samples from TCGA database. The analysis showed that the mRNA expression of neddylation pathway components was up-regulated in HCC and increased with disease severity. Moreover, we observed that activated neddylation pathway was associated with enriched infiltration of T helper 2 (Th2) cells in HCC, while transactivation of STAT5A signaling may mediate this association. On the contrary, no significant correlation between the neddylation pathway and Th1 cells infiltration was identified. Taken together, these findings suggest a potential role of the neddylation pathway in promoting a shift in Th1/Th2 balance toward Th2-dominant immunosuppression. Hence, targeting neddylation pathway could serve as an attractive immunotherapy strategy for suppressing the development of Th2 cells.Lisha ZhouLuyi ZhangSiyuan ChenDongsheng SunJianhua QuFrontiers Media S.A.articleneddylationTh2 cellsSTAT5Ahepatocellular carcinomaimmune responseNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neddylation Th2 cells STAT5A hepatocellular carcinoma immune response Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	neddylation Th2 cells STAT5A hepatocellular carcinoma immune response Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lisha Zhou Luyi Zhang Siyuan Chen Dongsheng Sun Jianhua Qu Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
description	Neddylation is a process in which a ubiquitin-like molecule NEDD8 is conjugated to a lysine residue of the substrate protein via successive enzymatic cascade reactions. Inactivation of neddylation pathway triggers tumor cell apoptosis or senescence to suppress the tumor growth. So far, there has been limited research on the role of the neddylation pathway (NEDD8-UBE2M-RBX1 axis) in the immune response. In this study, we investigated the association between the neddylation pathway and immune function in HCC by comprehensively analyzing transcriptome and clinical data of HCC samples from TCGA database. The analysis showed that the mRNA expression of neddylation pathway components was up-regulated in HCC and increased with disease severity. Moreover, we observed that activated neddylation pathway was associated with enriched infiltration of T helper 2 (Th2) cells in HCC, while transactivation of STAT5A signaling may mediate this association. On the contrary, no significant correlation between the neddylation pathway and Th1 cells infiltration was identified. Taken together, these findings suggest a potential role of the neddylation pathway in promoting a shift in Th1/Th2 balance toward Th2-dominant immunosuppression. Hence, targeting neddylation pathway could serve as an attractive immunotherapy strategy for suppressing the development of Th2 cells.
format	article
author	Lisha Zhou Luyi Zhang Siyuan Chen Dongsheng Sun Jianhua Qu
author_facet	Lisha Zhou Luyi Zhang Siyuan Chen Dongsheng Sun Jianhua Qu
author_sort	Lisha Zhou
title	Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
title_short	Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
title_full	Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
title_fullStr	Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
title_full_unstemmed	Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma
title_sort	elevated neddylation pathway promotes th2 cells infiltration by transactivating stat5a in hepatocellular carcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0af8430a758a4f4d948056a9211b00fb
work_keys_str_mv	AT lishazhou elevatedneddylationpathwaypromotesth2cellsinfiltrationbytransactivatingstat5ainhepatocellularcarcinoma AT luyizhang elevatedneddylationpathwaypromotesth2cellsinfiltrationbytransactivatingstat5ainhepatocellularcarcinoma AT siyuanchen elevatedneddylationpathwaypromotesth2cellsinfiltrationbytransactivatingstat5ainhepatocellularcarcinoma AT dongshengsun elevatedneddylationpathwaypromotesth2cellsinfiltrationbytransactivatingstat5ainhepatocellularcarcinoma AT jianhuaqu elevatedneddylationpathwaypromotesth2cellsinfiltrationbytransactivatingstat5ainhepatocellularcarcinoma
_version_	1718444269041090560

Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma

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