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组蛋白去乙酰化酶5通过上调Notch 1促进胶质瘤细胞增殖。

Histone deacetylase 5 promotes the proliferation of glioma cells by upregulation of Notch 1.

作者信息

Liu Quan, Zheng Jie-Min, Chen Jia-Kang, Yan Xian-Lei, Chen Hong-Mou, Nong Wei-Xia, Huang He-Qing

机构信息

Department of Neurosurgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, P.R. China.

Department of Histology and Embryology, School of Basic Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

出版信息

Mol Med Rep. 2014 Oct;10(4):2045-50. doi: 10.3892/mmr.2014.2395. Epub 2014 Jul 18.

Abstract

Histone deacetylases (HDACs) constitute a family of enzymes that play important roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation and apoptosis of cancer cells. However, the biological function of HDAC5 in glioma cells has not been fully understood. In the present study, we found that the mRNA and protein levels of HDAC5 are increased in human glioma tissues and cell lines. In addition, overexpression of HDAC5 promoted proliferation of glioma cells, as measured by the MTT assay. By contrast, HDAC5 gene silencing using small interfering RNA (siRNA) inhibited cell proliferation. Furthermore, we demonstrated that HDAC5 enhances Notch 1 expression at both the mRNA and the protein level in glioma cell lines. Taken together, these results demonstrated, for the first time to the best of our knowledge, that HDAC5 promotes glioma cell proliferation, and suggest that this effect involves the upregulation of Notch 1. Therefore, our study may provide a novel therapeutic target for treatment of gliomas.

摘要

组蛋白去乙酰化酶(HDACs)是一类在基因表达的表观遗传调控中发挥重要作用的酶,并且与癌细胞的生长、分化和凋亡有关。然而,HDAC5在胶质瘤细胞中的生物学功能尚未完全明确。在本研究中,我们发现HDAC5的mRNA和蛋白水平在人胶质瘤组织和细胞系中升高。此外,通过MTT法检测发现,HDAC5的过表达促进了胶质瘤细胞的增殖。相反,使用小干扰RNA(siRNA)沉默HDAC5基因可抑制细胞增殖。此外,我们证明HDAC5在mRNA和蛋白水平上均增强了胶质瘤细胞系中Notch 1的表达。据我们所知,这些结果首次证明HDAC5促进胶质瘤细胞增殖,并表明这种作用涉及Notch 1的上调。因此,我们的研究可能为胶质瘤的治疗提供一个新的治疗靶点。

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