title: Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma.
abstract: Systemic analyses using large-scale genomic profiles have successfully identified cancer-driving somatic copy number variations (SCNVs) loci. However, functions of vast focal SCNVs in "protein-coding gene desert" regions are largely unknown. The integrative analysis of long noncoding RNA (lncRNA) expression profiles with SCNVs in hepatocellular carcinoma (HCC) led us to identify the recurrent deletion of lncRNA-PRAL (p53 regulation-associated lncRNA) on chromosome 17p13.1, whose genomic alterations were significantly associated with reduced survival of HCC patients. We found that lncRNA-PRAL could inhibit HCC growth and induce apoptosis in vivo and in vitro through p53. Subsequent investigations indicated that the three stem-loop motifs at the 5' end of lncRNA-PRAL facilitated the combination of HSP90 and p53 and thus competitively inhibited MDM2-dependent p53 ubiquitination, resulting in enhanced p53 stability. Additionally, in vivo lncRNA-PRAL delivery efficiently reduced intrinsic tumors, indicating its potential therapeutic application.
  
  
  CONCLUSIONS
  lncRNA-PRAL, one of the key cancer-driving SCNVs, is a crucial stimulus for HCC growth and may serve as a potential target for antitumor therapy.
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chuan-chuan
authors.initials: CC
authors.lastname: Zhou
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Sheng-xian
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jin-zhao
authors.initials: JZ
authors.lastname: Ma
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Ji-hang
authors.initials: JH
authors.lastname: Yuan
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Feng-rui
authors.initials: FR
authors.lastname: Bi
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Kong-ying
authors.initials: KY
authors.lastname: Lin
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Yin
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Guang-wen
authors.initials: GW
authors.lastname: Cao
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Zhou
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Shu-han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002681:China / Q000453:epidemiology; D056905:Chromosome Breakpoints; D056915:DNA Copy Number Variations; D005260:Female; D016158:Genes, p53; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53