Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
School of Nursing, Chongqing College of Humanities, Science and Technology, Chongqing, China.
Cancer Biol Ther. 2024 Dec 31;25(1):2398297. doi: 10.1080/15384047.2024.2398297. Epub 2024 Sep 2.
Breast cancer ranks the first in the incidence of female cancer and is the most common cancer threatening the life and health of women worldwide.Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) is a pro-apoptotic gene downstream of p53. However, the role of TP53AIP1 in BC needs to be investigated. In vitro and in vivo experiments were conducted to assess the biological functions and associated mechanisms. Several bioinformatics analyses were made, CCK8 assay, wound healing, transwell assays, colony formation assay, EDU, flow cytometry, Immunofluorescence, qRT-PCR and Western-blotting were performed. In our study, we discovered that BC samples had low levels of TP53AIP1 expression, which correlated with a lower survival rate in BC patients. When TP53AIP1 was up-regulated, it caused a decrease in cell proliferation, migration, and invasion. It also induced epithelial-to-mesenchymal transition (EMT) and protective autophagy. Furthermore, the over-expression of TP53AIP1 suppressed tumor growth when tested in vivo. We also noticed that TP53AIP1 up-regulation resulted in decreased levels of phosphorylation in AKT and mTOR, suggesting a mechanistic role. In addition, we performed functional rescue experiments where the activation of AKT was able to counteract the impact of TP53AIP1 on the survival and autophagy in breast cancer cell lines. This suggests that TP53AIP1 acts as an oncogene by controlling the AKT/mTOR pathway. These findings reveal TP53AIP1 as a gene that suppresses tumor growth and triggers autophagy through the AKT/mTOR pathway in breast cancer cells. As a result, TP53AIP1 presents itself as a potential target for novel therapeutic approaches in treating breast cancer.
乳腺癌在女性癌症发病率中位居第一，是全球范围内威胁女性生命健康最常见的癌症。肿瘤抑制基因 p53 下游调控凋亡诱导蛋白 1（TP53AIP1）是一种促凋亡基因。然而，TP53AIP1 在乳腺癌中的作用尚需进一步研究。本研究通过体外和体内实验评估其生物学功能及相关机制，并进行了多项生物信息学分析。采用 CCK8 检测、划痕愈合实验、Transwell 实验、集落形成实验、EDU 实验、流式细胞术、免疫荧光实验、qRT-PCR 实验和 Western blot 实验进行检测。研究发现，乳腺癌组织中 TP53AIP1 表达水平降低，与乳腺癌患者生存率降低相关。上调 TP53AIP1 表达可抑制细胞增殖、迁移和侵袭，并诱导上皮间质转化（EMT）和保护性自噬。此外，体内实验表明过表达 TP53AIP1 可抑制肿瘤生长。研究还发现，TP53AIP1 过表达可降低 AKT 和 mTOR 的磷酸化水平，提示其发挥作用的机制。此外，本研究还进行了功能拯救实验，结果表明 AKT 的激活可逆转 TP53AIP1 对乳腺癌细胞系存活和自噬的影响。这表明 TP53AIP1 通过调控 AKT/mTOR 通路发挥致癌作用。综上，TP53AIP1 可通过 AKT/mTOR 通路抑制肿瘤生长并触发自噬，提示其可能成为治疗乳腺癌的潜在靶点。
