组蛋白乙酰转移酶 1 上调鼻咽癌细胞中 Bcl2L12 的表达。
Histone acetyltransferase 1 up regulates Bcl2L12 expression in nasopharyngeal cancer cells.
机构信息
Department of Otolaryngology, The First Affiliated Hospital, Shenzhen University, Shenzhen, China.
Department of Ophthalmology, The First Affiliated Hospital, Shenzhen University, Shenzhen, China.
出版信息
Arch Biochem Biophys. 2018 May 15;646:72-79. doi: 10.1016/j.abb.2018.03.040. Epub 2018 Apr 3.
The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry. The results showed that by screening the subtypes of HAT, the levels of HAT1 were uniquely higher in NPC as compared with non-cancer nasopharyngeal tissue. The levels of Bcl2L12 in NPC cells were positively correlated with HAT1. HAT1 involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment.
Bcl2L12 表达失调在癌症中已被认识到，但致病因素尚不清楚。组蛋白乙酰转移酶（HAT）在基因转录调控中发挥着关键作用。本研究检验了一个假说，即 HAT 的异常活性会导致鼻咽癌（NPC）中 Bcl2L12 的失调。在这项研究中，从临床收集了人鼻咽癌组织。通过实时 RT-PCR 和 Western blot 分析 NPC 细胞中 Bcl2L12 和 HATs 的表达。通过流式细胞术分析 NPC 细胞凋亡。结果表明，通过筛选 HAT 的亚型，与非癌性鼻咽组织相比，HAT1 在 NPC 中的水平独特地更高。NPC 细胞中 Bcl2L12 的水平与 HAT1 呈正相关。HAT1 参与 STAT5 与 Bcl2L12 启动子结合。HAT1 增加了 Bcl2L12 的表达。Bcl2L12 介导了 HAT1 对抑制 NPC 细胞凋亡的作用。吸收携带 HAT1 shRNA 质粒的脂质体诱导 NPC 细胞凋亡。总之，抑制 HAT1 可以通过增加 Bcl2L12 的表达诱导 NPC 细胞凋亡，这可能是 NPC 治疗的一种潜在疗法。
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