SP1-Mediated upregulation of CLEC18B promotes the proliferation and metastasis of glioma through regulation of the Wnt/β-Catenin/EMT Pathway

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-08-29 DOI:10.1016/j.tranon.2025.102515

Hongliang Liu , Bin Zhu , Yong Cui , Wei Liu , Qiang Xu , Xiangrui Lu , Zhaowen Tan , Yu Tian , Wei Xu

{"title":"SP1-Mediated upregulation of CLEC18B promotes the proliferation and metastasis of glioma through regulation of the Wnt/β-Catenin/EMT Pathway","authors":"Hongliang Liu , Bin Zhu , Yong Cui , Wei Liu , Qiang Xu , Xiangrui Lu , Zhaowen Tan , Yu Tian , Wei Xu","doi":"10.1016/j.tranon.2025.102515","DOIUrl":null,"url":null,"abstract":"<div><div>Glioma is one of the most aggressive and lethal brain tumors, with poor prognosis and limited treatment options. This study examined the function of CLEC18B in glioma development and its viability as a predictive biomarker. Pan-cancer research demonstrated that CLEC18B is dysregulated in several tumor types, with elevated expression associated with reduced overall survival (OS) and disease-specific survival (DSS) in patients with different malignancies, including glioma. CLEC18B was markedly increased in glioblastoma (GBM) and lower-grade glioma (LGG) tissues relative to normal tissues, and its elevated expression correlated with worse survival outcomes in both LGG and GBM patients. CLEC18B expression was an independent predictive indicator for OS and DSS in GBM, with expression levels being affected by DNA methylation status. We investigated the regulatory mechanisms governing CLEC18B expression and found SP1 as a major transcription factor that directly modulates CLEC18B. Our findings validated that SP1 associates with the CLEC18B promoter, and the silencing of SP1 resulted in a substantial decrease in CLEC18B expression. The suppression of CLEC18B functionally decreased glioma cell proliferation, motility, and invasion in vitro, and lowered tumor development in vivo. Furthermore, CLEC18B knockdown modified the Wnt/β-catenin/EMT signaling pathway by decreasing mesenchymal markers and increasing epithelial markers. Administration of a Wnt/β-catenin agonist partially mitigated the consequences of CLEC18B knockdown, indicating that CLEC18B facilitates glioma growth via the stimulation of this pathway. In conclusion, CLEC18B is crucial to glioma development, serving as a principal regulator of cell proliferation, migration, and invasion via the Wnt/β-catenin/EMT pathway. CLEC18B may function as a prospective prognostic biomarker and therapeutic target for glioma therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102515"},"PeriodicalIF":5.0000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523325002463","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Glioma is one of the most aggressive and lethal brain tumors, with poor prognosis and limited treatment options. This study examined the function of CLEC18B in glioma development and its viability as a predictive biomarker. Pan-cancer research demonstrated that CLEC18B is dysregulated in several tumor types, with elevated expression associated with reduced overall survival (OS) and disease-specific survival (DSS) in patients with different malignancies, including glioma. CLEC18B was markedly increased in glioblastoma (GBM) and lower-grade glioma (LGG) tissues relative to normal tissues, and its elevated expression correlated with worse survival outcomes in both LGG and GBM patients. CLEC18B expression was an independent predictive indicator for OS and DSS in GBM, with expression levels being affected by DNA methylation status. We investigated the regulatory mechanisms governing CLEC18B expression and found SP1 as a major transcription factor that directly modulates CLEC18B. Our findings validated that SP1 associates with the CLEC18B promoter, and the silencing of SP1 resulted in a substantial decrease in CLEC18B expression. The suppression of CLEC18B functionally decreased glioma cell proliferation, motility, and invasion in vitro, and lowered tumor development in vivo. Furthermore, CLEC18B knockdown modified the Wnt/β-catenin/EMT signaling pathway by decreasing mesenchymal markers and increasing epithelial markers. Administration of a Wnt/β-catenin agonist partially mitigated the consequences of CLEC18B knockdown, indicating that CLEC18B facilitates glioma growth via the stimulation of this pathway. In conclusion, CLEC18B is crucial to glioma development, serving as a principal regulator of cell proliferation, migration, and invasion via the Wnt/β-catenin/EMT pathway. CLEC18B may function as a prospective prognostic biomarker and therapeutic target for glioma therapy.

查看原文本刊更多论文

sp1介导的CLEC18B上调通过调控Wnt/β-Catenin/EMT通路促进胶质瘤的增殖和转移

胶质瘤是最具侵袭性和致死性的脑肿瘤之一，预后差，治疗选择有限。本研究检测了CLEC18B在胶质瘤发育中的功能及其作为预测性生物标志物的可行性。泛癌症研究表明，CLEC18B在多种肿瘤类型中表达失调，在包括胶质瘤在内的不同恶性肿瘤患者中，表达升高与总生存期（OS）和疾病特异性生存期（DSS）降低相关。与正常组织相比，cleec18b在胶质母细胞瘤（GBM）和低级别胶质瘤（LGG）组织中显著升高，其表达升高与LGG和GBM患者更差的生存结果相关。CLEC18B表达是GBM OS和DSS的独立预测指标，表达水平受DNA甲基化状态的影响。我们研究了控制CLEC18B表达的调控机制，发现SP1是直接调节CLEC18B的主要转录因子。我们的研究结果证实SP1与CLEC18B启动子相关，SP1的沉默导致CLEC18B表达的显著降低。抑制CLEC18B在体外功能上降低胶质瘤细胞的增殖、运动和侵袭，并降低肿瘤在体内的发展。此外，CLEC18B敲低通过降低间质标记物和增加上皮标记物来修饰Wnt/β-catenin/EMT信号通路。Wnt/β-catenin激动剂的使用部分减轻了CLEC18B敲低的后果，表明CLEC18B通过刺激这一途径促进胶质瘤的生长。总之，CLEC18B对胶质瘤的发展至关重要，它通过Wnt/β-catenin/EMT途径作为细胞增殖、迁移和侵袭的主要调节因子。CLEC18B可能作为神经胶质瘤治疗的前瞻性预后生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.