Liu Huantao, Wang He, Zhang Hongyu, Yu Miaomiao, Tang Yu
Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, China.
Department of Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, No.44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning Province, 110042, P. R. China.
Cancer Cell Int. 2024 Jun 12;24(1):207. doi: 10.1186/s12935-024-03384-4.
Globally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis.
TCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed.
TEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell.
TEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer.
在全球范围内，女性乳腺癌是癌症死亡的第五大主要原因。迫切需要探索乳腺癌增殖和转移的分子机制。
利用TCGA数据库分析乳腺癌和正常样本中的基因表达以及基因表达与预后的关联。采用免疫组织化学染色、qPCR和western印迹法检测基因表达。进行细胞功能试验，以研究异常表达的TEX19和CDK4对细胞增殖、迁移、凋亡、细胞周期和集落形成的影响。运用生物信息学分析方法并结合CHX追踪实验和Co-IP实验，筛选并验证TEX19的下游分子和调控机制。此外，构建裸鼠皮下肿瘤模型。
TEX19在乳腺癌中显著上调，且TEX19水平与肿瘤侵袭和预后相关。敲低TEX19可抑制乳腺癌细胞的增殖和迁移，增加细胞凋亡，并使细胞周期阻滞在G2期。此外，TEX19抑制体内肿瘤生长。机制上，TEX19上调CDK4蛋白水平，这依赖于E3泛素连接酶SKP2。具体而言，敲低TEX19和过表达SKP2蛋白破坏了CDK4蛋白的稳定性，增强了CDK4蛋白的泛素化。此外，敲低CDK4可抑制乳腺癌细胞的增殖、迁移和集落形成，并减轻TEX19过表达对乳腺癌细胞增殖和迁移的促进作用。
TEX19和CDK4在乳腺癌中上调，TEX19通过影响SKP2介导的CDK4泛素化增加CDK4蛋白水平，从而促进乳腺癌进展。
Zotero 插件
