Wang Yichao, Lu Hongsheng, Wang Zhongrong, Li Yueguo, Chen Xiaoying
Department of Clinical Laboratory Medicine, Taizhou Central Hospital (Taizhou Univesity Hospital), Taizhou, China.
Key Laboratory of Brain-Like Neuromorphic Devices and Systems of Hebei Province College of Electron and Information Engineering, Hebei University, Baoding, China.
Front Oncol. 2022 Apr 11;12:865067. doi: 10.3389/fonc.2022.865067. eCollection 2022.
Breast 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.
The 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.
We 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.
Our 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.
乳腺癌（BC）是一种常见的女性癌症，发病率和死亡率都很高。然而，BC的发病机制尚未完全阐明。研究表明，TGF-β1在调节肿瘤自噬和凋亡之间的平衡中起重要作用。我们旨在阐明自噬和凋亡在维持乳腺癌肿瘤微环境中的具体机制。
从TCGA数据库中检索850例BC患者的临床特征。通过Wilcox检验获得肿瘤组织和正常组织之间差异表达的自噬相关基因（DEARGs）。通过Cox比例风险回归分析构建预后风险模型，并通过ROC曲线进行验证。我们使用MDC染色、集落形成试验、CCK-8、流式细胞术分析来确认TGF-β1对乳腺癌细胞自噬和凋亡的重要性。此外，进行蛋白质免疫印迹以确定蛋白质的相对表达。利用Kaplan-Meier Plotter数据库确定TP63的预后价值。
我们成功构建了乳腺癌的预后风险模型，并筛选出一个自噬相关的预后基因——TP63。正如预期的那样，我们在JASPAR数据库中预测TGF-β1和TP63有一个结合位点。此外，TGF-β1通过抑制TP63的表达促进乳腺癌细胞的自噬并抑制其凋亡。
我们的研究证明了TGF-β/TP63信号通路在调节乳腺癌自噬和凋亡中的分子机制，并为乳腺癌提供了一个潜在的预后标志物。
