{"title":"SUZ12敲低通过抑制dnmt1介导的ZNF582启动子甲基化抑制口腔舌鳞癌的增殖、迁移和侵袭。","authors":"Xiangwei Kong, Yicheng Cheng, Lin Zhang, Wei Yin, Chenchen Wang, Zhan'ao Wu","doi":"10.1186/s12957-025-04015-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Suppressor of zest 12 (SUZ12) upregulation is related to cervical node metastasis in oral tongue squamous cell carcinoma (OTSCC). This study explored the roles and mechanism of SUZ12 in OTSCC progression.</p><p><strong>Methods: </strong>SUZ12 protein levels in OTSCC tissues and cell lines were determined using immunohistochemistry assay and Western blot analysis. SUZ12 was overexpressed or silenced through transfection of Overexpression plasmids or small interfering RNA targeting SUZ12 were transfected into CAL27 and SCC9 cells to achieve SUZ12 overexpression or knockdown. Subsequently, cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin) were determined. Zinc finger protein 582 (ZNF582) promoter methylation was detected using the methylation-specific PCR assay. Then, the effects of ZNF582 on CAL27 cell behaviors were also evaluated using gain/loss function experiments. Moreover, rescue experiments were conducted to investigate the role of the SUZ12/ZNF582 axis in regulating CAL27 cell progression. Additionally, SUZ12-silenced CAL27 cells were subcutaneously injected into the posterior flank of mice, followed by tumor growth detection within a 28 day period.</p><p><strong>Results: </strong>SUZ12 protein was significantly upregulated in OTSCC tissues and cell lines. SUZ12 overexpression augmented proliferation, migration, invasion and EMT in both CAL27 and SCC9 cells, while SUZ12 knockdown showed the opposite results. SUZ12 inhibited ZNF582 expression by promoting DNA methyltransferase 1 (DNMT1)-mediated ZNF582 promoter methylation. Moreover, ZNF582 knockdown promoted OTSCC cell proliferation, migration, invasion and EMT, while ZNF582 overexpression led to the opposite results. Rescue experiments demonstrated that ZNF582 knockdown abrogated SUZ12 knockdown-mediated inhibition of CAL27 cell malignant progression. Besides, SUZ12 knockdown suppressed xenograft tumor growth of OTSCC in nude mice.</p><p><strong>Conclusion: </strong>SUZ12 knockdown inhibits the proliferation, migration, invasion and EMT in OTSCC cells by inhibiting DNMT1-mediated ZNF582 promoter methylation, thereby suppressing tumor growth in vivo.</p>","PeriodicalId":23856,"journal":{"name":"World Journal of Surgical Oncology","volume":"23 1","pages":"350"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482123/pdf/","citationCount":"0","resultStr":"{\"title\":\"SUZ12 knockdown restrains the proliferation, migration, and invasion of oral tongue squamous cell carcinoma through inhibiting DNMT1-mediated ZNF582 promoter methylation.\",\"authors\":\"Xiangwei Kong, Yicheng Cheng, Lin Zhang, Wei Yin, Chenchen Wang, Zhan'ao Wu\",\"doi\":\"10.1186/s12957-025-04015-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Suppressor of zest 12 (SUZ12) upregulation is related to cervical node metastasis in oral tongue squamous cell carcinoma (OTSCC). This study explored the roles and mechanism of SUZ12 in OTSCC progression.</p><p><strong>Methods: </strong>SUZ12 protein levels in OTSCC tissues and cell lines were determined using immunohistochemistry assay and Western blot analysis. SUZ12 was overexpressed or silenced through transfection of Overexpression plasmids or small interfering RNA targeting SUZ12 were transfected into CAL27 and SCC9 cells to achieve SUZ12 overexpression or knockdown. Subsequently, cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin) were determined. Zinc finger protein 582 (ZNF582) promoter methylation was detected using the methylation-specific PCR assay. Then, the effects of ZNF582 on CAL27 cell behaviors were also evaluated using gain/loss function experiments. Moreover, rescue experiments were conducted to investigate the role of the SUZ12/ZNF582 axis in regulating CAL27 cell progression. Additionally, SUZ12-silenced CAL27 cells were subcutaneously injected into the posterior flank of mice, followed by tumor growth detection within a 28 day period.</p><p><strong>Results: </strong>SUZ12 protein was significantly upregulated in OTSCC tissues and cell lines. SUZ12 overexpression augmented proliferation, migration, invasion and EMT in both CAL27 and SCC9 cells, while SUZ12 knockdown showed the opposite results. SUZ12 inhibited ZNF582 expression by promoting DNA methyltransferase 1 (DNMT1)-mediated ZNF582 promoter methylation. Moreover, ZNF582 knockdown promoted OTSCC cell proliferation, migration, invasion and EMT, while ZNF582 overexpression led to the opposite results. Rescue experiments demonstrated that ZNF582 knockdown abrogated SUZ12 knockdown-mediated inhibition of CAL27 cell malignant progression. Besides, SUZ12 knockdown suppressed xenograft tumor growth of OTSCC in nude mice.</p><p><strong>Conclusion: </strong>SUZ12 knockdown inhibits the proliferation, migration, invasion and EMT in OTSCC cells by inhibiting DNMT1-mediated ZNF582 promoter methylation, thereby suppressing tumor growth in vivo.</p>\",\"PeriodicalId\":23856,\"journal\":{\"name\":\"World Journal of Surgical Oncology\",\"volume\":\"23 1\",\"pages\":\"350\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482123/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Surgical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12957-025-04015-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Surgical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12957-025-04015-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：zest抑制因子12 （Suppressor of zest 12, SUZ12）上调与口腔舌鳞癌（OTSCC）宫颈结转移有关。本研究探讨了SUZ12在OTSCC进展中的作用和机制。方法：采用免疫组化法和Western blot法检测OTSCC组织和细胞系中SUZ12蛋白水平。通过转染过表达质粒或将靶向SUZ12的小干扰RNA转染到CAL27和SCC9细胞中，实现SUZ12过表达或过表达沉默。随后，检测细胞增殖、迁移、侵袭和上皮-间质转化（EMT）标志物（E-cadherin、N-cadherin和Vimentin）。采用甲基化特异性PCR检测锌指蛋白582 （ZNF582）启动子甲基化。然后，通过增益/损失函数实验评估ZNF582对CAL27细胞行为的影响。此外，我们还通过挽救实验来研究SUZ12/ZNF582轴在调节CAL27细胞进展中的作用。此外，将suz12沉默的CAL27细胞皮下注射到小鼠后腹，随后在28天内检测肿瘤生长。结果：SUZ12蛋白在OTSCC组织和细胞系中显著上调。SUZ12过表达增强了CAL27和SCC9细胞的增殖、迁移、侵袭和EMT，而SUZ12敲低则显示相反的结果。SUZ12通过促进DNA甲基转移酶1 （DNMT1）介导的ZNF582启动子甲基化来抑制ZNF582的表达。此外，ZNF582敲低可促进OTSCC细胞的增殖、迁移、侵袭和EMT，而ZNF582过表达则相反。抢救实验表明，ZNF582敲除消除了SUZ12敲除介导的CAL27细胞恶性进展的抑制。此外，SUZ12基因敲低可抑制裸鼠OTSCC异种移植瘤的生长。结论：SUZ12敲低通过抑制dnmt1介导的ZNF582启动子甲基化，抑制OTSCC细胞的增殖、迁移、侵袭和EMT，从而抑制肿瘤生长。
SUZ12 knockdown restrains the proliferation, migration, and invasion of oral tongue squamous cell carcinoma through inhibiting DNMT1-mediated ZNF582 promoter methylation.
Background: Suppressor of zest 12 (SUZ12) upregulation is related to cervical node metastasis in oral tongue squamous cell carcinoma (OTSCC). This study explored the roles and mechanism of SUZ12 in OTSCC progression.
Methods: SUZ12 protein levels in OTSCC tissues and cell lines were determined using immunohistochemistry assay and Western blot analysis. SUZ12 was overexpressed or silenced through transfection of Overexpression plasmids or small interfering RNA targeting SUZ12 were transfected into CAL27 and SCC9 cells to achieve SUZ12 overexpression or knockdown. Subsequently, cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin) were determined. Zinc finger protein 582 (ZNF582) promoter methylation was detected using the methylation-specific PCR assay. Then, the effects of ZNF582 on CAL27 cell behaviors were also evaluated using gain/loss function experiments. Moreover, rescue experiments were conducted to investigate the role of the SUZ12/ZNF582 axis in regulating CAL27 cell progression. Additionally, SUZ12-silenced CAL27 cells were subcutaneously injected into the posterior flank of mice, followed by tumor growth detection within a 28 day period.
Results: SUZ12 protein was significantly upregulated in OTSCC tissues and cell lines. SUZ12 overexpression augmented proliferation, migration, invasion and EMT in both CAL27 and SCC9 cells, while SUZ12 knockdown showed the opposite results. SUZ12 inhibited ZNF582 expression by promoting DNA methyltransferase 1 (DNMT1)-mediated ZNF582 promoter methylation. Moreover, ZNF582 knockdown promoted OTSCC cell proliferation, migration, invasion and EMT, while ZNF582 overexpression led to the opposite results. Rescue experiments demonstrated that ZNF582 knockdown abrogated SUZ12 knockdown-mediated inhibition of CAL27 cell malignant progression. Besides, SUZ12 knockdown suppressed xenograft tumor growth of OTSCC in nude mice.
Conclusion: SUZ12 knockdown inhibits the proliferation, migration, invasion and EMT in OTSCC cells by inhibiting DNMT1-mediated ZNF582 promoter methylation, thereby suppressing tumor growth in vivo.
期刊介绍：
World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics.
Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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