Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma

Cervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial–mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motil...

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Autores principales:	Suna Zhou, Xuequan Wang, Jiapei Ding, Haihua Yang, Youyou Xie
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	autophagy-related genes Atg5 autophagy EMT cervical cancer prognosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/318c466eea954cfc943f571d9ce90eb6
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spelling	oai:doaj.org-article:318c466eea954cfc943f571d9ce90eb62021-12-01T01:12:03ZIncreased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma2296-634X10.3389/fcell.2021.757184https://doaj.org/article/318c466eea954cfc943f571d9ce90eb62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.757184/fullhttps://doaj.org/toc/2296-634XCervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial–mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motility. Autophagy-related genes (ARGs) are implicated in the EMT process, and autophagy exerts a dual function in EMT management at different phases of tumor progression. However, the role of specific ARGs during the EMT process has not yet been reported in cervical cancer. Based on the data from the Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) sequencing database, we performed the prognosis analysis for those ARGs obtained from the Human Autophagy database. ATG5 was identified as the only important harmful marker influencing survival of cervical cancer patients by univariate Cox regression (HR 1.7; 95% CI: 1.0–2.8, p = 0.047), and the 5-years survival rate for the high- and low-ATG5 expression groups was 0.486 (0.375–0.631) and 0.782 (0.708–0.863), respectively. TCGA CESC methylation data showed that eight methylation sites of ATG5 could also be significantly associated with the overall survival (OS) of cervical cancer patients. Single-sample gene-set enrichment and gene functional enrichment results showed that ATG5 was correlated with some cancer-related pathways, such as phagocytosis-related genes, endocytosis-related genes, immune-related genes, EMT score, and some EMT signature-related genes. Next, cell migration and invasion assay and Western blot were applied to detect the function of ATG5 in EMT of cervical cancer. In cervical cancer cells, ATG5 knockdown resulted in attenuation of migration and invasion. The functional study showed that knockdown of ATG5 could reverse EMT process by P-ERK, P-NFκBp65, P-mTOR pathways, and so on. In conclusion, the present study implies that ATG5 was a major contributor to EMT regulation and poor prognosis in cervical cancer.Suna ZhouSuna ZhouXuequan WangXuequan WangJiapei DingJiapei DingHaihua YangHaihua YangYouyou XieYouyou XieFrontiers Media S.A.articleautophagy-related genesAtg5autophagyEMTcervical cancerprognosisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy-related genes Atg5 autophagy EMT cervical cancer prognosis Biology (General) QH301-705.5
spellingShingle	autophagy-related genes Atg5 autophagy EMT cervical cancer prognosis Biology (General) QH301-705.5 Suna Zhou Suna Zhou Xuequan Wang Xuequan Wang Jiapei Ding Jiapei Ding Haihua Yang Haihua Yang Youyou Xie Youyou Xie Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
description	Cervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial–mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motility. Autophagy-related genes (ARGs) are implicated in the EMT process, and autophagy exerts a dual function in EMT management at different phases of tumor progression. However, the role of specific ARGs during the EMT process has not yet been reported in cervical cancer. Based on the data from the Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) sequencing database, we performed the prognosis analysis for those ARGs obtained from the Human Autophagy database. ATG5 was identified as the only important harmful marker influencing survival of cervical cancer patients by univariate Cox regression (HR 1.7; 95% CI: 1.0–2.8, p = 0.047), and the 5-years survival rate for the high- and low-ATG5 expression groups was 0.486 (0.375–0.631) and 0.782 (0.708–0.863), respectively. TCGA CESC methylation data showed that eight methylation sites of ATG5 could also be significantly associated with the overall survival (OS) of cervical cancer patients. Single-sample gene-set enrichment and gene functional enrichment results showed that ATG5 was correlated with some cancer-related pathways, such as phagocytosis-related genes, endocytosis-related genes, immune-related genes, EMT score, and some EMT signature-related genes. Next, cell migration and invasion assay and Western blot were applied to detect the function of ATG5 in EMT of cervical cancer. In cervical cancer cells, ATG5 knockdown resulted in attenuation of migration and invasion. The functional study showed that knockdown of ATG5 could reverse EMT process by P-ERK, P-NFκBp65, P-mTOR pathways, and so on. In conclusion, the present study implies that ATG5 was a major contributor to EMT regulation and poor prognosis in cervical cancer.
format	article
author	Suna Zhou Suna Zhou Xuequan Wang Xuequan Wang Jiapei Ding Jiapei Ding Haihua Yang Haihua Yang Youyou Xie Youyou Xie
author_facet	Suna Zhou Suna Zhou Xuequan Wang Xuequan Wang Jiapei Ding Jiapei Ding Haihua Yang Haihua Yang Youyou Xie Youyou Xie
author_sort	Suna Zhou
title	Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
title_short	Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
title_full	Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
title_fullStr	Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
title_full_unstemmed	Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma
title_sort	increased atg5 expression predicts poor prognosis and promotes emt in cervical carcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/318c466eea954cfc943f571d9ce90eb6
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_version_	1718406014452105216

Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma

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