组蛋白去乙酰化酶1对胃癌干细胞增殖分化的影响及机制

发布时间：2018-07-11 09:57

本文选题：HDAC1 + 胃癌干细胞　；参考：《安徽医科大学》2017年硕士论文

【摘要】：背景与目的:胃癌干细胞是近年来的研究热点,胃癌干细胞的增殖分化与胃癌的转移及预后有密切关联。组蛋白的乙酰化修饰在胚胎干细胞增殖分化过程中起着非常重要的作用,组蛋白去乙酰化酶1(HDAC1)对胃癌干细胞增值分化的影响及机制未见报导,本研究拟通过慢病毒转染敲低胃癌干细胞观察HDAC1表达对人类胃癌干细胞干性增殖、迁移及侵袭的影响以及对胃癌干细胞干性相关基因表达的影响,进一步探讨HDAC1低表达对人类胃癌干细胞增殖分化的影响及机制。方法:以Nanog为胃癌细胞干性标志物,流式细胞术筛选出胃癌干细胞。通过慢病毒转染技术干扰胃癌干细胞中HDAC1表达,实时定量PCR(qRT-PCR)和Western Blot方法检测干扰效率。采用MTT比色法和划痕试验分别观察两组细胞增殖和迁移能力的差异;通过transwell实验观察两组细胞侵袭能力的差异;采用RT-qPCR和Western Blot方法检测两组细胞干性相关基因表达。结果:HDAC1在实验组胃癌干细胞中的表达显著低于对照组(p0.05);实验组细胞的增殖、迁移和侵袭能力显著低于对照组(p0.05);实验组细胞干性相关基因表达显著低于对照组(p0.05)。结论:HDAC1低表达降低了胃癌干细胞的增殖、迁移及侵袭能力;HDAC1低表达下调了BMi1基因表达可能是其降低胃癌干细胞的增殖、干性及侵袭的机制之一。
[Abstract]:Background & objective: gastric cancer stem cells have been a hot topic in recent years. The proliferation and differentiation of gastric cancer stem cells are closely related to the metastasis and prognosis of gastric cancer. The acetylation modification of histone plays an important role in the proliferation and differentiation of embryonic stem cells. The effect of histone deacetylase 1 (HDAC1) on the proliferation and differentiation of gastric cancer stem cells has not been reported. In this study, the effects of HDAC1 expression on dry proliferation, migration and invasion of human gastric cancer stem cells and the expression of genes related to dry nature of gastric cancer stem cells were observed by lentivirus transfection and low knockout of gastric cancer stem cells. To investigate the effect and mechanism of HDAC1 low expression on the proliferation and differentiation of human gastric cancer stem cells. Methods: gastric cancer stem cells were screened by flow cytometry with Nanog as the dry marker of gastric cancer cells. The expression of HDAC1 in gastric cancer stem cells was inhibited by lentivirus transfection, and the interference efficiency was detected by real-time quantitative PCR (qRT-PCR) and Western blot. MTT colorimetric assay and scratch assay were used to observe the difference of cell proliferation and migration ability, transwell assay was used to observe the difference of cell invasion ability, and RT-qPCR and Western Blot were used to detect the expression of dry-related genes in the two groups. Results the expression of cell weight HDAC1 in gastric cancer stem cells in the experimental group was significantly lower than that in the control group (p0.05), the proliferation, migration and invasion ability of the cells in the experimental group was significantly lower than that in the control group (p0.05), and the expression of dry-related genes in the experimental group was significantly lower than that in the control group (p0.05). Conclusion the low expression of HDAC1 reduces the proliferation of gastric cancer stem cells, and the down-regulation of BMI1 gene expression may be one of the mechanisms that reduce the proliferation, dryness and invasion of gastric cancer stem cells.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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