Zhen Xiao, Jiayi Li, Shuxia Fan, Yu Wang, Qingsong Jin
{"title":"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。","authors":"Zhen Xiao, Jiayi Li, Shuxia Fan, Yu Wang, Qingsong Jin","doi":"10.1007/s10616-025-00787-7","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>+</sup>CD86<sup>+</sup> 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<i>.</i> 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.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-025-00787-7.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 4","pages":"123"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165943/pdf/","citationCount":"0","resultStr":"{\"title\":\"Transcription factor SP1 drives the malignant progression of oral squamous cell carcinoma and M2 macrophage polarization through transcription activation-mediated upregulation CLEC7A.\",\"authors\":\"Zhen Xiao, Jiayi Li, Shuxia Fan, Yu Wang, Qingsong Jin\",\"doi\":\"10.1007/s10616-025-00787-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sup>+</sup>CD86<sup>+</sup> 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<i>.</i> 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.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-025-00787-7.</p>\",\"PeriodicalId\":10890,\"journal\":{\"name\":\"Cytotechnology\",\"volume\":\"77 4\",\"pages\":\"123\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165943/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytotechnology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s10616-025-00787-7\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-025-00787-7","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Transcription factor SP1 drives the malignant progression of oral squamous cell carcinoma and M2 macrophage polarization through transcription activation-mediated upregulation CLEC7A.
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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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.
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