Zhao Luguang, He Dan, Jiao Mengmeng, Kong Lingshuo, Shao Chunkui, Chen Junli, Fang Zhigang, Ma Xiaohui, Chen Huifang, Li Lin, Luo Si, Zheng Na, Chen Yunbo, Wang Qi, Fang Shuhuan
1 DME Center, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
2 Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Technol Cancer Res Treat. 2017 Oct;16(5):586-594. doi: 10.1177/1533034616661664. Epub 2016 Aug 9.
Epigenetic modifications are involved in the pathogenesis of cancer, and histone deacetylase inhibitors are considered potential therapeutic agents. Histone tails undergo acetylation at lysine residues, which is associated with transcriptional activation. However, previous studies indicated that as histone deacetylase inhibitors, both (-)-epigallocatechin-3-gallate and valproic acid presented the effects of downregulation of amyloid precursor protein expression, which resulted in the induction of apoptosis. The downregulation of amyloid precursor protein, instead of conventionally activating gene expression as histone deacetylase inhibitor, was attractive. However, there was no relevant report on the correlation of the expression of amyloid precursor protein and histone deacetylase 1 in cancer. In the present study, we detected the expression of amyloid precursor protein and histone deacetylase 1 in hepatocellular carcinoma and adjacent tissues, as well as the correlations among histone deacetylase 1, amyloid precursor protein, and tumor stage. The results showed that the expressions of amyloid precursor protein and histone deacetylase 1 were significantly higher in hepatocellular carcinoma tissues than that in adjacent tissues ( P < .05), however, there was no statistical difference between amyloid precursor protein and histone deacetylase 1 with tumor stages. The present findings provided more foundation for the study on amyloid precursor protein metabolism in cancer, especially on the regulation of amyloid precursor protein by histone deacetylases.
表观遗传修饰参与癌症的发病机制,组蛋白脱乙酰酶抑制剂被认为是潜在的治疗药物。组蛋白尾部在赖氨酸残基处发生乙酰化,这与转录激活相关。然而,先前的研究表明,作为组蛋白脱乙酰酶抑制剂,(-)-表没食子儿茶素-3-没食子酸酯和丙戊酸均呈现出淀粉样前体蛋白表达下调的作用,这导致了细胞凋亡的诱导。淀粉样前体蛋白的下调,并非像组蛋白脱乙酰酶抑制剂那样传统地激活基因表达,这一点很吸引人。然而,关于癌症中淀粉样前体蛋白表达与组蛋白脱乙酰酶1之间的相关性,尚无相关报道。在本研究中,我们检测了肝细胞癌及癌旁组织中淀粉样前体蛋白和组蛋白脱乙酰酶1的表达,以及组蛋白脱乙酰酶1、淀粉样前体蛋白与肿瘤分期之间的相关性。结果显示,肝细胞癌组织中淀粉样前体蛋白和组蛋白脱乙酰酶1的表达显著高于癌旁组织(P <.05),然而,淀粉样前体蛋白和组蛋白脱乙酰酶1与肿瘤分期之间无统计学差异。本研究结果为癌症中淀粉样前体蛋白代谢的研究,尤其是组蛋白脱乙酰酶对淀粉样前体蛋白的调控研究,提供了更多的依据。