在骨肉瘤中,上调HDAC9通过抑制p53转录促进细胞增殖。

IF 0.2 Q4 MEDICINE, RESEARCH & EXPERIMENTAL International journal of clinical and experimental medicine Pub Date : 2015-07-15 eCollection Date: 2015-01-01
Yu-Xin Zhao, Yi-Sheng Wang, Qi-Qing Cai, Jia-Qiang Wang, Wei-Tao Yao
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引用次数: 0

摘要

越来越多的研究表明,组蛋白去乙酰化酶(histone deacetylases, hdac)的表达改变通过上调或下调参与细胞增殖、细胞周期调控和细胞凋亡的关键基因,在肿瘤发生中起着至关重要的作用。本研究探讨了HDAC9在骨肉瘤中的表达及功能。实时荧光定量PCR和Western blot分析发现,与相邻正常组织相比,HDAC9在骨肉瘤组织中表达上调。体外研究进一步表明,在U2OS和MG63细胞中过表达HDAC9可促进细胞增殖和侵袭。通过染色质免疫沉淀(ChIP)实验,我们发现HDAC9通过结合其近端启动子区来抑制p53的转录。因此,我们的数据表明HDAC9/p53调控通路在骨肉瘤的进展中起重要作用。
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Up-regulation of HDAC9 promotes cell proliferation through suppressing p53 transcription in osteosarcoma.

Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up-regulation or down-regulation of key genes involved in cell proliferation, cell-cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression.

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