Transcription factor SP1 drives the malignant progression of oral squamous cell carcinoma and M2 macrophage polarization through transcription activation-mediated upregulation CLEC7A.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-08-01 Epub Date: 2025-06-13 DOI:10.1007/s10616-025-00787-7

Zhen Xiao, Jiayi Li, Shuxia Fan, Yu Wang, Qingsong Jin

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引用次数: 0

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Previous studies have suggested that C-Type Lectin Domain Containing 7A (CLEC7A) could affect human cancer progression by regulating M2 macrophage polarization. However, the role of the molecular mechanism of CLEC7A involved in OSCC progression is poorly defined. GEPIA database was used to analyze CLEC7A and specificity protein 1 (SP1) expression, and the relationship between CLEC7A and M2-type macrophage markers (CD163 and MRC1). CLEC7A and SP1 levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). CLEC7A, SP1, RHOA, RAC1, E-cadherin, and Vimentin protein levels were detected using western blot. Cell proliferation, apoptosis, migration, and invasion were detected by Colony formation, flow cytometry, and Transwell assays. The proportion of CD11b⁺CD86⁺ positive cells was detected using flow cytometry. Binding between SP1 and CLEC7A promoter was predicted by JASPAR, and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The biological role of SP1 on OSCC tumor growth was examined by the xenograft tumor model in vivo. CLEC7A and SP1 expression levels were increased in OSCC tissues and cell lines. Furthermore, CLEC7A deficiency could repress OSCC cell proliferation, migration, invasion, M2-type macrophage polarization, and induce cell apoptosis in vitro, as well as hinder tumor growth in vivo. At the molecular level, SP1 was a transcription factor of CLEC7A and promoted CLEC7A transcription via binding to its promoter regions. SP1-activated CLEC7A could facilitate OSCC cell malignant behaviors and M2 macrophage polarization, providing a possible therapeutic target for OSCC treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00787-7.

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转录因子SP1通过转录激活介导的CLEC7A上调，驱动口腔鳞状细胞癌的恶性进展和M2巨噬细胞极化。

口腔鳞状细胞癌（OSCC）是口腔最常见的恶性肿瘤。先前的研究表明，C-Type Lectin Domain Containing 7A （CLEC7A）可能通过调节M2巨噬细胞极化影响人类癌症的进展。然而，CLEC7A参与OSCC进展的分子机制的作用尚不明确。采用GEPIA数据库分析cleec7a与特异性蛋白1 （SP1）的表达，以及cleec7a与m2型巨噬细胞标志物（CD163、MRC1）的关系。采用实时定量聚合酶链反应（RT-qPCR）检测cle7a和SP1水平。western blot检测cle7a、SP1、RHOA、RAC1、E-cadherin、Vimentin蛋白水平。通过集落形成、流式细胞术和Transwell实验检测细胞增殖、凋亡、迁移和侵袭。流式细胞术检测CD11b+CD86+阳性细胞比例。SP1与cle7a启动子的结合通过JASPAR预测，并通过染色质免疫沉淀（ChIP）和双荧光素酶报告基因检测进行验证。通过体内异种移植肿瘤模型研究SP1对OSCC肿瘤生长的生物学作用。cle7a和SP1在OSCC组织和细胞系中的表达水平升高。cle7a缺乏在体外可抑制OSCC细胞的增殖、迁移、侵袭、m2型巨噬细胞极化、诱导细胞凋亡，在体内可抑制肿瘤生长。在分子水平上，SP1是CLEC7A的转录因子，通过与CLEC7A的启动子区结合促进其转录。sp1活化的CLEC7A可促进OSCC细胞的恶性行为和M2巨噬细胞极化，为OSCC治疗提供可能的治疗靶点。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00787-7获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.