Cheng Guangcun, He Jie, Zhang Leilei, Ge Shengfang, Zhang He, Fan Xianqun
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Tumour Biol. 2016 Sep;37(9):12779-12789. doi: 10.1007/s13277-016-5243-3. Epub 2016 Jul 23.
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. Although the diagnosis modality of primary UM was improved significantly, there are currently no effective therapies for metastatic UM. Hypermethylated in cancer 1 (HIC1) is frequently deleted or epigenetically silenced in various human cancers. However, the role and mechanism of HIC1 in UM is still unclear. In this study, we found that HIC1 acted as a tumor suppressor and that its expression was downregulated in UM. Functional studies demonstrated that ectopic expression of HIC1 in UM cells inhibited cell proliferation and invasion. Moreover, through long non-coding RNA (lncRNA) microarray and real-time PCR, we found that expression of lncRNA-numb was activated by HIC1 in UM. The results provide evidence that lncRNA-numb is a newly proposed tumor suppressor that is involved in HIC1-induced phenotypes. Taken together, our studies of UM reveal a critical role of HIC1 in the regulation of tumorigenesis, at least partly through its downstream target, lncRNA-numb, and provide a potential therapeutic target for UM.
葡萄膜黑色素瘤（UM）是成人中最常见的原发性眼内癌。尽管原发性UM的诊断方式有了显著改善，但目前对于转移性UM尚无有效的治疗方法。癌症1中高甲基化（HIC1）在各种人类癌症中经常缺失或发生表观遗传沉默。然而，HIC1在UM中的作用和机制仍不清楚。在本研究中，我们发现HIC1作为一种肿瘤抑制因子，其在UM中的表达下调。功能研究表明，在UM细胞中异位表达HIC1可抑制细胞增殖和侵袭。此外，通过长链非编码RNA（lncRNA）微阵列和实时PCR，我们发现在UM中lncRNA-numb的表达受HIC1激活。这些结果提供了证据，表明lncRNA-numb是一种新提出的肿瘤抑制因子，参与HIC1诱导的表型。综上所述，我们对UM的研究揭示了HIC1在肿瘤发生调控中的关键作用，至少部分是通过其下游靶点lncRNA-numb实现的，并为UM提供了一个潜在的治疗靶点。
