Wang Beibei, Zhang Qingsong, Wang Lihua, Su Huiwen, Zhou Li, Zhang Rong, Wan Qiangkun
Department of Gynecological Oncology, The 1st Affiliated Hospital of Bengbu Medical University, Bengbu, China.
The 1st Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):6009-6020. doi: 10.1007/s00210-024-03680-w. Epub 2024 Dec 3.
Cervical squamous cell carcinoma (CSCC) poses a significant health challenge, especially in developing countries. Identifying novel prognostic biomarkers and potential drug targets is crucial for improving CSCC management. We analyzed ADAMDEC1 expression patterns in CSCC using various bioinformatic datasets. Clinical samples from CSCC patients were evaluated for ADAMDEC1 and TYMP levels through Western blot and qRT-PCR. Multiple in vitro techniques, including flow cytometry, CCK-8, Transwell, Western blot, wound healing assays, and Co-IP, were employed to investigate the role and molecular pathways associated with ADAMDEC1. Our findings reveal that ADAMDEC1 is significantly overexpressed in CSCC tissues compared to adjacent healthy tissues. Functional assays demonstrated that ADAMDEC1 overexpression significantly enhances cell proliferation, migration, and invasion in vitro, while concurrently inhibiting apoptosis. Conversely, the knockdown of ADAMDEC1 reversed these effects, leading to reduced cell proliferation and increased apoptosis. Mechanistically, we identified a direct interaction between ADAMDEC1 and TYMP, which activates the JAK/STAT signaling pathway in CSCC cells. This activation was confirmed through Western blot analysis, indicating increased phosphorylation of JAK1 and STAT3 in response to ADAMDEC1 overexpression. ADAMDEC1 promotes CSCC progression by modulating the JAK/STAT pathway through regulation of TYMP. These findings suggest that ADAMDEC1 could serve as a molecular biomarker for early diagnosis and targeted therapy in CSCC.
宫颈鳞状细胞癌（CSCC）对健康构成重大挑战，尤其是在发展中国家。识别新的预后生物标志物和潜在的药物靶点对于改善CSCC的治疗至关重要。我们使用各种生物信息学数据集分析了CSCC中ADAMDEC1的表达模式。通过蛋白质免疫印迹法（Western blot）和实时定量逆转录聚合酶链反应（qRT-PCR）评估了CSCC患者临床样本中的ADAMDEC1和胸苷磷酸化酶（TYMP）水平。采用了多种体外技术，包括流式细胞术、CCK-8、Transwell、蛋白质免疫印迹法、伤口愈合试验和免疫共沉淀（Co-IP），以研究与ADAMDEC1相关的作用和分子途径。我们的研究结果表明，与相邻的健康组织相比，ADAMDEC1在CSCC组织中显著过表达。功能试验表明，ADAMDEC1的过表达显著增强了体外细胞的增殖、迁移和侵袭，同时抑制了细胞凋亡。相反，敲低ADAMDEC1可逆转这些作用，导致细胞增殖减少和细胞凋亡增加。从机制上讲，我们发现ADAMDEC1与TYMP之间存在直接相互作用，这激活了CSCC细胞中的JAK/STAT信号通路。通过蛋白质免疫印迹分析证实了这种激活，表明响应于ADAMDEC1的过表达，JAK1和STAT3的磷酸化增加。ADAMDEC1通过调节TYMP来调节JAK/STAT通路，从而促进CSCC的进展。这些发现表明，ADAMDEC1可作为CSCC早期诊断和靶向治疗的分子生物标志物。
