Cao Li, Jing Xintao, Liu Lijuan, Wang Hui, Zhu Jiaqi, Zhou Jing, Peng Hang, Zhang Jinyuan, Li Fang, Wang Xiaofei, Zhao Le
Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
Heliyon. 2024 Aug 4;10(15):e35695. doi: 10.1016/j.heliyon.2024.e35695. eCollection 2024 Aug 15.
MZT2A is a novel core component in the γ-tubulin ring complex and aberrantly expressed in some types of tumors. However, MZT2A expression pattern across different cancers and its role in kidney renal clear cell carcinoma have not been sufficiently investigated. A thorough analysis of MZT2A expression landscape across 33 cancer types was conducted, utilizing 712 normal samples and 9807 tumor samples from TCGA (version 37.0), as well as 5112 normal samples from the GTEx databases. MZT2A's impact on KIRC cell viability and proliferation were evaluated through BrdU assays and monitored by cell imaging readers in MZT2A-expressing plasmid or siRNA-transfected cells. Additionally, the effects of MZT2A on cell apoptosis and cell cycle were detected using flow cytometry and Western blot. WGCNA analysis was employed to construct a co-expression gene network associated with MZT2A expression in KIRC, and Pearson correlation coefficient was utilized to examine the relationships between pairs of genes. MZT2A is overexpressed in 25 out of 33 types of cancer, including KIRC. In KIRC, high level of MZT2A was associated with higher clinical stage progression and poorer patients' survival. Downregulation of MZT2A decreased KIRC cell proliferation, retarded cell cycle and promoted apoptosis, while upregulation of MZT2A produced the opposite effects. WGCNA analysis and in vitro experiments revealed that MZT2A activated PI3K/AKT signaling pathway in KIRC. In all, MZT2A was overexpressed in most types of tumors. MZT2A served as an oncogene in KIRC and might be a potential target for guiding future treatments.
MZT2A是γ-微管蛋白环复合物中的一种新型核心成分，在某些类型的肿瘤中异常表达。然而，MZT2A在不同癌症中的表达模式及其在肾透明细胞癌中的作用尚未得到充分研究。利用来自TCGA（版本37.0）的712个正常样本和9807个肿瘤样本以及来自GTEx数据库的5112个正常样本，对33种癌症类型中MZT2A的表达情况进行了全面分析。通过BrdU检测评估MZT2A对肾透明细胞癌（KIRC）细胞活力和增殖的影响，并在转染了MZT2A表达质粒或小干扰RNA（siRNA）的细胞中通过细胞成像读数仪进行监测。此外，使用流式细胞术和蛋白质免疫印迹法检测MZT2A对细胞凋亡和细胞周期的影响。采用加权基因共表达网络分析（WGCNA）构建与KIRC中MZT2A表达相关的共表达基因网络，并利用皮尔逊相关系数检验基因对之间的关系。MZT2A在33种癌症类型中的25种中过表达，包括KIRC。在KIRC中，高水平的MZT2A与更高的临床分期进展和更差的患者生存率相关。下调MZT2A可降低KIRC细胞增殖、延缓细胞周期并促进细胞凋亡，而上调MZT2A则产生相反的效果。WGCNA分析和体外实验表明，MZT2A在KIRC中激活了PI3K/AKT信号通路。总之，MZT2A在大多数类型的肿瘤中过表达。MZT2A在KIRC中作为一种癌基因发挥作用，可能是指导未来治疗的潜在靶点。
