转录因子 Sp3 对 CSTB 基因表达的转录激活。
Transcriptional activation of CSTB gene expression by transcription factor Sp3.
机构信息
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
出版信息
Biochem Biophys Res Commun. 2023 Mar 15;649:71-78. doi: 10.1016/j.bbrc.2023.01.087. Epub 2023 Jan 30.
CSTB has been reported to be associated with the pathogenesis of many malignant tumors, especially hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated is largely unknown. We initially cloned and analyzed the promoter region of the CSTB gene by luciferase assay and the Sp3 binding site (CCCCGCCCCGCG) was found in it. The results of electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments verified that the transcription factor, Sp3 could bind to the " CCCCGCCCCGCG ″ site of the CSTB gene promoter. We showed that the overexpression of Sp3 significantly increased the endogenous mRNA and protein expression levels of CSTB, whereas knockdown of Sp3 decreased the mRNA and protein expression levels according to quantitative real-time PCR (qRT‒PCR) and western blotting. In conclusion, CSTB gene expression is closely regulated by transcription factor Sp3, which may be a potential mechanism for the dysregulation of CSTB expression in HCC.
CSTB 已被报道与许多恶性肿瘤的发病机制有关，特别是肝细胞癌（HCC）。然而，该基因的表达如何被调控在很大程度上仍是未知的。我们最初通过荧光素酶检测克隆并分析了 CSTB 基因的启动子区域，在其中发现了 Sp3 结合位点（CCCCGCCCCGCG）。电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）实验的结果证实转录因子 Sp3 可以与 CSTB 基因启动子上的“CCCCGCCCCGCG”位点结合。我们发现 Sp3 的过表达显著增加了 CSTB 的内源性 mRNA 和蛋白表达水平，而根据定量实时 PCR（qRT-PCR）和 Western blot 分析，Sp3 的敲低则降低了 CSTB 的 mRNA 和蛋白表达水平。总之，CSTB 基因的表达受到转录因子 Sp3 的紧密调控，这可能是 HCC 中 CSTB 表达失调的潜在机制。
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