title: HIC1 modulates uveal melanoma progression by activating lncRNA-numb.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhanghe@sjtu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. fanxq@sh163.net.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding
keywords: HIC1; Long non-coding RNA; Numb; Uveal melanoma