TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63

BackgroundBreast cancer (BC) is a prevalent female cancer, which has high morbidity and mortality. However, the pathogenesis of BC has not been fully elucidated. Studies have shown that TGF-β1 plays an important role in regulating the balance between autophagy and apoptosis of tumor. We aim to clari...

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Main Authors: Yichao Wang, Hongsheng Lu, Zhongrong Wang, Yueguo Li, Xiaoying Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.865067/full
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author Yichao Wang
Hongsheng Lu
Zhongrong Wang
Yueguo Li
Xiaoying Chen
author_facet Yichao Wang
Hongsheng Lu
Zhongrong Wang
Yueguo Li
Xiaoying Chen
author_sort Yichao Wang
collection DOAJ
description BackgroundBreast cancer (BC) is a prevalent female cancer, which has high morbidity and mortality. However, the pathogenesis of BC has not been fully elucidated. Studies have shown that TGF-β1 plays an important role in regulating the balance between autophagy and apoptosis of tumor. We aim to clarify the specific mechanism of autophagy and apoptosis in breast cancer maintaining the tumor microenvironment.MethodsThe clinical characteristics of 850 BC patients were retrieved from the TCGA database. Differentially expressed autophagy-related genes (DEARGs) between tumor and normal tissues were obtained by the Wilcox test. Through Cox proportional hazard regression analysis, the prognostic risk model was constructed and verified by the ROC curve. We used MDC staining, colony formation assay, CCK-8, flow cytometric analysis to confirm the importance of TGF-β1 on the autophagy and apoptosis of breast cancer cells. Furthermore, western blot was performed to determine the relative expression of protein. The Kaplan-Meier Plotter database was utilized to identify the prognostic value of TP63.ResultsWe successfully constructed a prognostic risk model of breast cancer and screened out an autophagy-related prognostic gene -TP63. We predicted that TGF-β1 and TP63 have a binding site in the JASPAR database as expected. Additionally, TGF-β1 promoted autophagy and inhibited apoptosis of breast cancer cells by inhibiting the expression of TP63.ConclusionOur study demonstrated that the molecular mechanism of TGF-β/TP63 signaling in regulating autophagy and apoptosis of breast cancer and provided a potential prognostic marker in breast cancer.
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spelling doaj.art-be43fe300e3742e98946d20934b7a0fb2022-12-22T03:03:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.865067865067TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63Yichao Wang0Hongsheng Lu1Zhongrong Wang2Yueguo Li3Xiaoying Chen4Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou Univesity Hospital), Taizhou, ChinaDepartment of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou Univesity Hospital), Taizhou, ChinaKey Laboratory of Brain-Like Neuromorphic Devices and Systems of Hebei Province College of Electron and Information Engineering, Hebei University, Baoding, ChinaDepartment of Clinical Laboratory, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou Univesity Hospital), Taizhou, ChinaBackgroundBreast cancer (BC) is a prevalent female cancer, which has high morbidity and mortality. However, the pathogenesis of BC has not been fully elucidated. Studies have shown that TGF-β1 plays an important role in regulating the balance between autophagy and apoptosis of tumor. We aim to clarify the specific mechanism of autophagy and apoptosis in breast cancer maintaining the tumor microenvironment.MethodsThe clinical characteristics of 850 BC patients were retrieved from the TCGA database. Differentially expressed autophagy-related genes (DEARGs) between tumor and normal tissues were obtained by the Wilcox test. Through Cox proportional hazard regression analysis, the prognostic risk model was constructed and verified by the ROC curve. We used MDC staining, colony formation assay, CCK-8, flow cytometric analysis to confirm the importance of TGF-β1 on the autophagy and apoptosis of breast cancer cells. Furthermore, western blot was performed to determine the relative expression of protein. The Kaplan-Meier Plotter database was utilized to identify the prognostic value of TP63.ResultsWe successfully constructed a prognostic risk model of breast cancer and screened out an autophagy-related prognostic gene -TP63. We predicted that TGF-β1 and TP63 have a binding site in the JASPAR database as expected. Additionally, TGF-β1 promoted autophagy and inhibited apoptosis of breast cancer cells by inhibiting the expression of TP63.ConclusionOur study demonstrated that the molecular mechanism of TGF-β/TP63 signaling in regulating autophagy and apoptosis of breast cancer and provided a potential prognostic marker in breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.865067/fullautophagy-related genesTGF-β1TP63autophagyapoptosisbreast cancer
spellingShingle Yichao Wang
Hongsheng Lu
Zhongrong Wang
Yueguo Li
Xiaoying Chen
TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
Frontiers in Oncology
autophagy-related genes
TGF-β1
TP63
autophagy
apoptosis
breast cancer
title TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
title_full TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
title_fullStr TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
title_full_unstemmed TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
title_short TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
title_sort tgf β1 promotes autophagy and inhibits apoptosis in breast cancer by targeting tp63
topic autophagy-related genes
TGF-β1
TP63
autophagy
apoptosis
breast cancer
url https://www.frontiersin.org/articles/10.3389/fonc.2022.865067/full
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