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c-myb是血细胞生成过程中的一个重要转录因子,与造血干细胞的增殖、分化、凋亡有关。在白血病、结肠癌、乳腺癌和黑色素瘤等恶性肿瘤中,c-myb异常表达,但是在白血病细胞中c-myb调控的机制尚不清楚。本研究探究了U937细胞中GATA1与c-myb的调控关系,可能对白血病研究和治疗提供帮助。用12-氧-十四烷酰佛波醇-13-乙酸酯(TPA)诱导U937细胞分化,并检测分化前后GATA1与c-myb蛋白的变化。Western blot结果显示U937细胞经TPA诱导分化后c-myb与GATA1蛋白均明显下降。利用慢病毒包装GATA1 shRNA质粒和GATA1过表达质粒并感染到U937细胞中实现转录因子GATA1的敲降及过表达后,检测c-myb的m RNA和蛋白的表达水平。结果显示:敲降GATA1后,c-myb的m RNA和蛋白质水平明显下降;过表达GATA1后,c-myb的m RNA和蛋白质水平明显上调。本研究揭示了U937细胞中GATA1对c-myb的正向调控关系,为白血病研究和治疗方案提供了新的思路。
Abstract：c-myb is an important transcription factor in the process of hematopoiesis and is related to the proliferation, differentiation and apoptosis of hematopoietic stem cells. In malignant tumors such as leukemia, colon cancer, breast cancer and melanoma, c-myb is abnormally expressed, but the mechanism of c-myb regulation in leukemia cells is unclear. This study explored the relationship between GATA1 and c-myb in U937 cells. Regulating the relationship may help leukemia research and treatment. The differentiation of U937 cells was induced with12-O-tetradecanoylphorbol-13-acetate(TPA), and the expressions of GATA1 and c-myb protein before and after differentiation were detected. Western blot results showed that c-myb and GATA1 protein decreased significantly after U937 cell differentiation induced by TPA. After lentivirus packaging GATA1 shRNA plasmid and GATA1 overexpression plasmid and infecting U937 cells to achieve knockdown and overexpression of transcription factor GATA1, the expression levels of c-myb mRNA and protein were detected. The results showed that after knocking down GATA1, the mRNA and protein levels of c-myb decreased significantly; after overexpressing GATA1, the m RNA and protein levels of c-myb increased significantly. Our research revealed the positive regulation of c-myb by GATA1 in U937 cells, and provided new ideas for leukemia research and treatment options.
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基本信息:
DOI：10.13417/j.gab.040.001339
中图分类号:R329.2
引用信息:
[1]程凯,张众,李梦佳,等.U937细胞中GATA1调控c-myb基因表达[J].基因组学与应用生物学,2021,40(03):1339-1347.DOI:10.13417/j.gab.040.001339.
基金信息:
国家自然科学基金项目(81770165)资助
2021-03-25
2021-03-25