1α,25(OH)2D3诱导SKOV-3细胞CYP24A1上调相关基因表达谱分析
首发时间:2018-04-27
摘要:目的:通过检测活性维生素D(1α,25-dihydroxy-vitaminD3, 1α,25(OH)2D3)对人卵巢癌细胞SKOV-3基因表达谱的改变,从中分析差异基因与1α,25(OH)2D3代谢酶CYP24A1之间的关系,探讨CYP24A1减弱1α,25(OH)2D3抑制肿瘤细胞增殖和迁移能力的相关分子机制。方法:应用基因芯片技术 检测1α,25(OH)2D3(100 nmol/L)处理组SKOV-3与空白对照组的基因表达,以CYP24A1表达模式为参考,对差异基因进行共表达分析。通过 Gene Ontology (GO)以及KEGG pathway数据库对差异表达基因进行基因信息学分析。结果:1α,25(OH)2D3使SKOV-3细胞基因表达谱发生显著改变,与CYP24A1基因共表达的差异基因有39个,其中33个基因表达上调,6个基因表达下调。MAP7D2是上调倍数最高的基因,IGF1是下调倍数最高的基因。结论:CYP24A1可能通过改变KIT、TRPV6、IGFBP3、GRK5、IGFBP1等差异基因的表达,影响信号转导、细胞蛋白代谢过程、细胞增殖等生物过程,以及干细胞多能性调控、TGF-β 信号通路、p53信号通路等分子机制,从而减弱了1α,25(OH)2D3抑制细胞增殖和迁移过程。
关键词: 1α,25(OH)2D3 CYP24A1 基因表达谱 SKOV-3
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Expression profiles of genes associated with up regulation of CYP24A1 induced by 1α,25(OH)2D3 in SKOV-3 cells
Abstract:Objective: In this paper to investigate the differences of the gene expression profiles in human ovarian cancer cells SKOV-3 with active vitamin D (1α,25-dihydroxy-vitaminD3, 1α,25(OH)2D3), and to analyze the relationship between differential genes and 1α,25(OH)2D3 metabolic enzyme CYP24A1, and to explore the molecular mechanism of CYP24A1 weakening the ability of 1α,25(OH)2D3 to inhibit the proliferation and migration of tumor cells. Methods: Gene chips were used to investigate the gene expression of 1α,25(OH)2D3 treatment group and blank control group. Based on the CYP24A1 expression pattern, we co-expression analyzed the differentially expressed genes. And the differential expression genes were analyzed through Gene Ontology (GO) and KEGG pathway database. Results: Among the differentially expressed genes, there were 39 co-expressed with CYP24A1 gene, among which, up- and down-regulated genes were 33 and 6, respectively. MAP7D2 was the most up-regulated gene, and IGF1 was the most down-regulated gene. Conclusion: CYP24A1 may affect the expression of differentially expressed genes such as KIT, TRPV6, IGFBP3, GRK5, IGFBP1, and also affect the biological processes such as siExpression profiles of genes associated with up regulation of CYP24A1 induced by 1α,25(OH)2D3 in ovarian cancer SKOV-3 cellsgnal transduction, cellular protein metabolism process, cell proliferation, as well as the molecular mechanisms of signaling pathways regulating pluripotency of stem cells, TGF-β signaling pathway, p53 signaling pathway and so on, thus reducing the inhibition of 1α,25(OH)2D3 to ovarian cancer cell proliferation and migration.
Keywords: 1α,25(OH)2D3 CYP24A1 Gene expression profiles SKOV-3
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1α,25(OH)2D3诱导SKOV-3细胞CYP24A1上调相关基因表达谱分析
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