ADAMDEC1通过调节TYMP增强JAK/STAT信号通路,促进宫颈鳞癌的发生。

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Beibei Wang, Qingsong Zhang, Lihua Wang, Huiwen Su, Li Zhou, Rong Zhang, Qiangkun Wan
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引用次数: 0

摘要

宫颈鳞状细胞癌(CSCC)是一个重大的健康挑战,特别是在发展中国家。确定新的预后生物标志物和潜在的药物靶点对于改善CSCC的管理至关重要。我们使用各种生物信息学数据集分析了ADAMDEC1在CSCC中的表达模式。采用Western blot和qRT-PCR检测CSCC患者临床样本ADAMDEC1和TYMP水平。采用多种体外技术,包括流式细胞术、CCK-8、Transwell、Western blot、伤口愈合试验和Co-IP,研究了ADAMDEC1的作用和相关的分子途径。我们的研究结果显示,与邻近的健康组织相比,ADAMDEC1在CSCC组织中显着过表达。功能分析表明,ADAMDEC1过表达可显著增强体外细胞增殖、迁移和侵袭,同时抑制细胞凋亡。相反,ADAMDEC1的敲低逆转了这些作用,导致细胞增殖减少和细胞凋亡增加。在机制上,我们确定了ADAMDEC1和TYMP之间的直接相互作用,其激活CSCC细胞中的JAK/STAT信号通路。通过Western blot分析证实了这种激活,表明在ADAMDEC1过表达的反应中,JAK1和STAT3的磷酸化增加。ADAMDEC1通过调控TYMP调控JAK/STAT通路促进CSCC进展。这些发现提示ADAMDEC1可作为CSCC早期诊断和靶向治疗的分子生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ADAMDEC1 promotes cervical squamous cell carcinoma by enhancing the JAK/STAT signaling pathway through modulation of TYMP.

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.

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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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