Yu Jing, Yuan Zhenlong, Liu Jing, Deng Lu, Zhao Yuting, Wang Shengnan, Tang Enyu, Yang Xi, Li Ning, An Jusheng, Wu Lingying
Department of Gynecology Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Biomedicines. 2024 Jul 3;12(7):1468. doi: 10.3390/biomedicines12071468.
Cervical squamous cell carcinoma (CSCC) represents a significant global health concern among females. Identifying new biomarkers and therapeutic targets is pivotal for improving the prognosis of CSCC. This study investigates the prognostic relevance of CCZ1 in CSCC and elucidates its downstream pathways and targets using a combination of bioinformatics analysis and experimental validation. Transcriptomic analysis of 239 CSCC and 3 normal cervical samples from The Cancer Genome Atlas database reveals a marked upregulation of CCZ1 mRNA levels in CSCC, and elevated CCZ1 mRNA levels were associated with poor prognosis. Immunohistochemical analysis of clinical samples also confirmed these findings. Furthermore, functional assays, including Cell Counting Kit-8, colony formation, Transwell, and flow cytometry, elucidated the influence of CCZ1 on CSCC cell proliferation, migration, invasion, and cell cycle progression. Remarkably, CCZ1 knockdown suppressed CSCC progression both in vitro and in vivo. Mechanistically, CCZ1 knockdown downregulated MMP2 and MMP17 expression. Restoring MMP2 or MMP17 expression rescued phenotypic alterations induced by CCZ1 knockdown. Hence, CCZ1 promotes CSCC progression by upregulating MMP2 and MMP17 expression, emerging as a novel biomarker in CSCC and presenting potential as a therapeutic target in CSCC.
宫颈鳞状细胞癌(CSCC)是全球女性健康面临的重大问题。识别新的生物标志物和治疗靶点对于改善CSCC的预后至关重要。本研究通过生物信息学分析和实验验证相结合的方法,探讨了CCZ1在CSCC中的预后相关性,并阐明了其下游途径和靶点。对来自癌症基因组图谱数据库的239例CSCC和3例正常宫颈样本进行转录组分析,结果显示CSCC中CCZ1 mRNA水平显著上调,且CCZ1 mRNA水平升高与预后不良相关。对临床样本的免疫组织化学分析也证实了这些发现。此外,通过细胞计数试剂盒-8、集落形成、Transwell和流式细胞术等功能实验,阐明了CCZ1对CSCC细胞增殖、迁移、侵袭和细胞周期进程的影响。值得注意的是,CCZ1基因敲低在体外和体内均抑制了CSCC的进展。机制上,CCZ1基因敲低下调了MMP2和MMP17的表达。恢复MMP2或MMP17的表达可挽救由CCZ1基因敲低诱导的表型改变。因此,CCZ1通过上调MMP2和MMP17的表达促进CSCC进展,成为CSCC中的一种新型生物标志物,并具有作为CSCC治疗靶点的潜力。