Department of Ophthalmology, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China.
Xi'an Medical University, Xi'an, 710086, China.
Cell Death Dis. 2023 Jan 18;14(1):38. doi: 10.1038/s41419-022-05522-0.
Choroidal melanoma (CM) is the most common type of diagnosed uveal melanoma (UM), which is prone to metastasis and exhibits a poor prognosis. The molecular mechanisms underlying CM progression need further elucidation to research effective therapeutic strategies. Histone deacetylase 7 (HDAC7) is very important in regulating cancer progression, but the significance and effect of HDAC7 on CM progression are unclear. In the present study, we found that HDAC7 is overexpressed in CM tissues versus normal tissues. We built HDAC7 overexpressing CM cell lines to study the functions of HDAC7 in CM progression and verified that upregulation of HDAC7 promoted the proliferation and metastasis of CM cells, while pharmacological inhibition of HDAC7 suppressed both the proliferation and metastasis of CM cells. Furthermore, we found that the aforementioned cancer-promoting effect of HDAC7 was mediated by c-Myc. Targeted inhibition of c-Myc inhibited CM progression by interfering with the HDAC7/c-Myc signaling pathway. Our study highlighted the function of targeting the HDAC7/c-Myc signaling pathway to intervene in the pathological process of CM, which provides potential therapeutic strategies for CM treatment.
脉络膜黑色素瘤 (CM) 是最常见的诊断性葡萄膜黑色素瘤 (UM) 类型，易发生转移，预后不良。CM 进展的分子机制需要进一步阐明，以研究有效的治疗策略。组蛋白去乙酰化酶 7 (HDAC7) 在调节癌症进展方面非常重要，但 HDAC7 对 CM 进展的意义和影响尚不清楚。在本研究中，我们发现 HDAC7 在 CM 组织中过度表达，而在正常组织中表达较低。我们构建了 HDAC7 过表达的 CM 细胞系，以研究 HDAC7 在 CM 进展中的功能，并验证了上调 HDAC7 促进了 CM 细胞的增殖和转移，而 HDAC7 的药理学抑制则抑制了 CM 细胞的增殖和转移。此外，我们发现 HDAC7 的上述促癌作用是通过 c-Myc 介导的。靶向抑制 c-Myc 通过干扰 HDAC7/c-Myc 信号通路抑制 CM 进展。我们的研究强调了靶向 HDAC7/c-Myc 信号通路干预 CM 病理过程的功能，为 CM 治疗提供了潜在的治疗策略。
