Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells

Intrahepatic cholangiocarcinoma is the second most common primary liver tumor with increasing incidence worldwide. Metabolic reprogramming caused by metabolic related gene disorders is a prominent hallmark of tumors, among which Glycogen Synthase 2 (GYS2) is the key gene responsible for regulating c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sigen A, Huijun Wu, Xiaodong Wang, Xidong Wang, Jiarui Yang, Long Xia, Yijun Xia
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	intrahepatic cholangiocarcinoma glycogen synthase 2 prognosis p53 signaling pathway Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/45a90d9ad03f4d1cacdeca0c0a3144e7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:45a90d9ad03f4d1cacdeca0c0a3144e7
record_format	dspace
spelling	oai:doaj.org-article:45a90d9ad03f4d1cacdeca0c0a3144e72021-11-17T14:21:59ZValue of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells2165-59792165-598710.1080/21655979.2021.2005224https://doaj.org/article/45a90d9ad03f4d1cacdeca0c0a3144e72021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005224https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Intrahepatic cholangiocarcinoma is the second most common primary liver tumor with increasing incidence worldwide. Metabolic reprogramming caused by metabolic related gene disorders is a prominent hallmark of tumors, among which Glycogen Synthase 2 (GYS2) is the key gene responsible for regulating cellular energy metabolism, and its expression disorders are closely related to various tumors and glycometabolic diseases. However, we still know nothing about its role in intrahepatic cholangiocarcinoma. The purpose of this study was to uncover the functional role of GYS2 in the progression ICC and explore the underlying mechanism. Firstly, we performed an integrated pan-cancer analysis of GYS2 in the Gene Expression Profiling Interactive Analysis database and further detected the expression of GYS2 in paired intrahepatic cholangiocarcinoma and adjacent non-tumor tissues by qPCR, then we analyzed the relationship between the expression level and clinicopathologic factors as well as the effect on the survival of patients. Finally, we identified the effect on the biological behavior of cholangiocarcinoma cells by cellular and molecular experiments. The expression of GYS2 was significantly downregulated in intrahepatic cholangiocarcinoma. The low expression of GYS2 was not only associated with the degree of pathological differentiation, tumor size, microvascular invasion and lymph node metastasis, but also an independent risk factor for unfavorable prognosis. Functional studies have shown that GYS2 overexpression can significantly impair the proliferation, replication, cloning, migration and invasion of cholangiocarcinoma cells, while the silencing GYS2 dramatically promotes the development of the aforementioned phenotypes, the underlying mechanism may be that GYS2 activates the P53 pathway. In conclusions, low GYS2 expression in intrahepatic cholangiocarcinoma predicted unfavorable patient outcomes; GYS2 overexpression can significantly impair the proliferation, migration and invasion of cholangiocarcinoma cells via activating the P53 pathway and GYS2 was expected to become a potential therapeutic target for such patients.Sigen AHuijun WuXiaodong WangXidong WangJiarui YangLong XiaYijun XiaTaylor & Francis Grouparticleintrahepatic cholangiocarcinomaglycogen synthase 2prognosisp53 signaling pathwayBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intrahepatic cholangiocarcinoma glycogen synthase 2 prognosis p53 signaling pathway Biotechnology TP248.13-248.65
spellingShingle	intrahepatic cholangiocarcinoma glycogen synthase 2 prognosis p53 signaling pathway Biotechnology TP248.13-248.65 Sigen A Huijun Wu Xiaodong Wang Xidong Wang Jiarui Yang Long Xia Yijun Xia Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
description	Intrahepatic cholangiocarcinoma is the second most common primary liver tumor with increasing incidence worldwide. Metabolic reprogramming caused by metabolic related gene disorders is a prominent hallmark of tumors, among which Glycogen Synthase 2 (GYS2) is the key gene responsible for regulating cellular energy metabolism, and its expression disorders are closely related to various tumors and glycometabolic diseases. However, we still know nothing about its role in intrahepatic cholangiocarcinoma. The purpose of this study was to uncover the functional role of GYS2 in the progression ICC and explore the underlying mechanism. Firstly, we performed an integrated pan-cancer analysis of GYS2 in the Gene Expression Profiling Interactive Analysis database and further detected the expression of GYS2 in paired intrahepatic cholangiocarcinoma and adjacent non-tumor tissues by qPCR, then we analyzed the relationship between the expression level and clinicopathologic factors as well as the effect on the survival of patients. Finally, we identified the effect on the biological behavior of cholangiocarcinoma cells by cellular and molecular experiments. The expression of GYS2 was significantly downregulated in intrahepatic cholangiocarcinoma. The low expression of GYS2 was not only associated with the degree of pathological differentiation, tumor size, microvascular invasion and lymph node metastasis, but also an independent risk factor for unfavorable prognosis. Functional studies have shown that GYS2 overexpression can significantly impair the proliferation, replication, cloning, migration and invasion of cholangiocarcinoma cells, while the silencing GYS2 dramatically promotes the development of the aforementioned phenotypes, the underlying mechanism may be that GYS2 activates the P53 pathway. In conclusions, low GYS2 expression in intrahepatic cholangiocarcinoma predicted unfavorable patient outcomes; GYS2 overexpression can significantly impair the proliferation, migration and invasion of cholangiocarcinoma cells via activating the P53 pathway and GYS2 was expected to become a potential therapeutic target for such patients.
format	article
author	Sigen A Huijun Wu Xiaodong Wang Xidong Wang Jiarui Yang Long Xia Yijun Xia
author_facet	Sigen A Huijun Wu Xiaodong Wang Xidong Wang Jiarui Yang Long Xia Yijun Xia
author_sort	Sigen A
title	Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
title_short	Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
title_full	Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
title_fullStr	Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
title_full_unstemmed	Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
title_sort	value of glycogen synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/45a90d9ad03f4d1cacdeca0c0a3144e7
work_keys_str_mv	AT sigena valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT huijunwu valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT xiaodongwang valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT xidongwang valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT jiaruiyang valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT longxia valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells AT yijunxia valueofglycogensynthase2inintrahepaticcholangiocarcinomaprognosisassessmentanditsinfluenceontheactivityofcancercells
_version_	1718425411958865920

Value of Glycogen Synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells

Ejemplares similares