title: ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma.
abstract: Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a "domino effect-like" therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspicious INK4b-ARF-INK4a gene cluster at chromosome 9p21, aberrant INK4a and INK4b defects were simultaneously endogenously auto-corrected after targeting the suppression of abnormal ANRIL lncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrant INK4-hub.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Shiqiong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Huixue
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yingyun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: zhanghe@sjtu.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: drfanxianqun@126.com.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays; D000098943:Uveal Melanoma
chemical_list: C000614131:CDKN2A protein, human; C561518:CDKN2B antisense RNA, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D062085:RNA, Long Noncoding
keywords: ANRIL; INK4A; INK4B; Melanoma; Therapeutic efficacy