EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 i...

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Autores principales:	Yu-Gang Huang, Ya Wang, Rui-Juan Zhu, Kai Tang, Xian-Bin Tang, Xiao-Min Su
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	adrenocortical carcinoma ACC ESM1 DLL4 Notch signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1db52a3b64954620ab0cf39d75ffb95c
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spelling	oai:doaj.org-article:1db52a3b64954620ab0cf39d75ffb95c2021-11-10T08:04:46ZEMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma2234-943X10.3389/fonc.2021.771579https://doaj.org/article/1db52a3b64954620ab0cf39d75ffb95c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.771579/fullhttps://doaj.org/toc/2234-943XAdrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.Yu-Gang HuangYa WangRui-Juan ZhuKai TangXian-Bin TangXiao-Min SuFrontiers Media S.A.articleadrenocortical carcinomaACCESM1DLL4Notch signaling pathwayNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adrenocortical carcinoma ACC ESM1 DLL4 Notch signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	adrenocortical carcinoma ACC ESM1 DLL4 Notch signaling pathway Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yu-Gang Huang Ya Wang Rui-Juan Zhu Kai Tang Xian-Bin Tang Xiao-Min Su EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
description	Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.
format	article
author	Yu-Gang Huang Ya Wang Rui-Juan Zhu Kai Tang Xian-Bin Tang Xiao-Min Su
author_facet	Yu-Gang Huang Ya Wang Rui-Juan Zhu Kai Tang Xian-Bin Tang Xiao-Min Su
author_sort	Yu-Gang Huang
title	EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
title_short	EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
title_full	EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
title_fullStr	EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
title_full_unstemmed	EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma
title_sort	ems1/dll4-notch signaling axis augments cell cycle-mediated tumorigenesis and progress in human adrenocortical carcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1db52a3b64954620ab0cf39d75ffb95c
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EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma

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