Gong Dan, Zeng Zhiwen, Yi Fengming, Wu Jianbing
Department of Oncology, Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Department of Oncology, Third Hospital of Nanchang Nanchang 330009, China.
Am J Transl Res. 2019 Feb 15;11(2):983-990. eCollection 2019.
The apoptosis machinery is compromised in liver cancer (LC). The underlying mechanism needs to be further investigated. Histone deacetylases (HDAC) have multiple and strong biochemical activities. This study tests a hypothesis that HDAC11 prevents LC cell (LCC) apoptosis via modulating the p53 gene transcription. In this study, the LC tissues were collected from patients with LC. The LCCs were purified by magnetic cell sorting. The gene transcription activities of the LCCs were analyzed by immunoprecipitation (IP) and chromatin IP. We observed that the LCCs expressed high levels of HDAC11, which was negatively correlated with the expression of p53 in LCCs. Further findings indicated that HDAC11 formed a complex with Egr1, the transcription factor of p53. HDAC11 induced Egr1 deacetylation and thus prevented the p53 gene transcription. Over expression of HDAC11 in liver cells inhibited the cell apoptosis. Inhibition of the expression of HDAC11 in LCCs promoted the LCC apoptosis. In conclusion, HDAC11 plays a critical role in the compromising the expression p53 in LCC, which can be reversed by the inhibition of HDAC11. To regulate HDAC11 may have therapeutic potential for LC treatment.
肝癌（LC）中的细胞凋亡机制受损。其潜在机制有待进一步研究。组蛋白脱乙酰酶（HDAC）具有多种强大的生化活性。本研究检验了一个假设，即HDAC11通过调节p53基因转录来阻止肝癌细胞（LCC）凋亡。在本研究中，从肝癌患者身上收集了肝组织。通过磁性细胞分选纯化LCC。通过免疫沉淀（IP）和染色质IP分析LCC的基因转录活性。我们观察到LCC中HDAC11表达水平较高，这与LCC中p53的表达呈负相关。进一步的研究结果表明，HDAC11与p53的转录因子Egr1形成复合物。HDAC11诱导Egr1去乙酰化，从而阻止p53基因转录。肝细胞中HDAC11的过表达抑制细胞凋亡。LCC中HDAC11表达的抑制促进了LCC凋亡。总之，HDAC11在损害LCC中p53表达方面起关键作用，抑制HDAC11可逆转这一作用。调节HDAC11可能对肝癌治疗具有潜在的治疗价值。
