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Abstract：
BACKGROUND: Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the role of SETDB1 in OC.
METHODS: GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC.
RESULTS: In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer.
CONCLUSIONS: SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC.
METHODS: GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC.
RESULTS: In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer.
CONCLUSIONS: SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC.
摘要：
背景：卵巢癌（OC）是最致命的妇科恶性肿瘤。促进OC启动和进展的机制尚不清楚。SET结构域分叉的组蛋白赖氨酸甲基转移酶1（SETDB1）在多种肿瘤中充当癌基因。本研究旨在探讨SETDB1在OC中的作用。
方法：GEO，TCGA,CSIOVDB和CPTAC数据库联合分析了SETDBlmRNA和蛋白质表达。通过在线Kaplan-Meier绘图仪和CSIOVDB数据库分析SETDB1表达对OC患者临床预后的影响。然后，使用MTT检查SETDB1在OC细胞进展和迁移率中的作用，EdU,集落形成和transwell测定。此外,CistromeDB数据库用于可视化SETDB1蛋白和剪接因子3b亚基4（SF3B4）启动子的结合，并进行双荧光素酶报告基因测定以确认相互作用。最后,采用生物信息学分析揭示了SETDB1与OC微环境的关系。
结果：在本研究中，我们发现，在OC中SETDB1明显上调，其过度表达预示着OC患者预后不良。然后，我们验证了SETDB1在体外促进OC细胞的进展和运动。SETDB1的击倒具有相反的效果。进一步研究表明SETDB1作为转录因子激活SF3B4的表达。SF3B4敲低削弱了SETDB1促进OC细胞增殖能力和运动的作用。最后,生物信息学分析结果证实SETDB1调控卵巢癌的免疫微环境。
结论：SETDB1通过上调SF3B4的表达和抑制肿瘤免疫，促进卵巢癌的进展。SETDB1可能是OC的有希望的预后和治疗标志物。
方法：GEO，TCGA,CSIOVDB和CPTAC数据库联合分析了SETDBlmRNA和蛋白质表达。通过在线Kaplan-Meier绘图仪和CSIOVDB数据库分析SETDB1表达对OC患者临床预后的影响。然后，使用MTT检查SETDB1在OC细胞进展和迁移率中的作用，EdU,集落形成和transwell测定。此外,CistromeDB数据库用于可视化SETDB1蛋白和剪接因子3b亚基4（SF3B4）启动子的结合，并进行双荧光素酶报告基因测定以确认相互作用。最后,采用生物信息学分析揭示了SETDB1与OC微环境的关系。
结果：在本研究中，我们发现，在OC中SETDB1明显上调，其过度表达预示着OC患者预后不良。然后，我们验证了SETDB1在体外促进OC细胞的进展和运动。SETDB1的击倒具有相反的效果。进一步研究表明SETDB1作为转录因子激活SF3B4的表达。SF3B4敲低削弱了SETDB1促进OC细胞增殖能力和运动的作用。最后,生物信息学分析结果证实SETDB1调控卵巢癌的免疫微环境。
结论：SETDB1通过上调SF3B4的表达和抑制肿瘤免疫，促进卵巢癌的进展。SETDB1可能是OC的有希望的预后和治疗标志物。
