Long Noncoding RNA, Polycomb, and the Ghosts Haunting INK4b-ARF-INK4a Expression

被引:216
作者
Aguilo, Francesca [1 ,2 ]
Zhou, Ming-Ming [1 ]
Walsh, Martin J. [1 ,2 ,3 ]
机构
[1] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA
[3] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA
关键词
TUMOR-SUPPRESSOR LOCUS; METHYLATED HISTONE H3; INK4A; ANRIL; CBX7; COMPLEXES; CELLS;
D O I
10.1158/0008-5472.CAN-10-4379
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15(INK4b), p14(ARF), and p16(INK4a), and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development. Cancer Res; 71(16); 5365-9. (c) 2011 AACR.
引用
收藏
页码:5365 / 5369
页数:5
相关论文
共 30 条
  • [1] Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia:: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour
    Astuti, D
    Latif, F
    Wagner, K
    Gentle, D
    Cooper, WN
    Catchpoole, D
    Grundy, R
    Ferguson-Smith, AC
    Maher, ER
    [J]. BRITISH JOURNAL OF CANCER, 2005, 92 (08) : 1574 - 1580
  • [2] RETRACTED: CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus (Retracted Article)
    Bernard, D
    Martinez-Leal, JF
    Rizzo, S
    Martinez, D
    Hudson, D
    Visakorpi, T
    Peters, G
    Carnero, A
    Beach, D
    Gil, J
    [J]. ONCOGENE, 2005, 24 (36) : 5543 - 5551
  • [3] Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin
    Bernstein, E
    Duncan, EM
    Masui, O
    Gil, J
    Heard, E
    Allis, CD
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (07) : 2560 - 2569
  • [4] Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk
    Burd, Christin E.
    Jeck, William R.
    Liu, Yan
    Sanoff, Hanna K.
    Wang, Zefeng
    Sharpless, Norman E.
    [J]. PLOS GENETICS, 2010, 6 (12) : 1 - 15
  • [5] Role of histone H3 lysine 27 methylation in polycomb-group silencing
    Cao, R
    Wang, LJ
    Wang, HB
    Xia, L
    Erdjument-Bromage, H
    Tempst, P
    Jones, RS
    Zhang, Y
    [J]. SCIENCE, 2002, 298 (5595) : 1039 - 1043
  • [6] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression
    Cunnington, Michael S.
    Koref, Mauro Santibanez
    Mayosi, Bongani M.
    Burn, John
    Keavney, Bernard
    [J]. PLOS GENETICS, 2010, 6 (04):
  • [7] Role for the MOV10 RNA helicase in Polycomb-mediated repression of the INK4a tumor suppressor
    El Messaoudi-Aubert, Selma
    Nicholls, James
    Maertens, Goedele N.
    Brookes, Sharon
    Bernstein, Emily
    Peters, Gordon
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (07) : 862 - U112
  • [8] Polycomb CBX7 has a unifying role in cellular lifespan
    Gil, J
    Bernard, D
    Martínez, D
    Beach, D
    [J]. NATURE CELL BIOLOGY, 2004, 6 (01) : 67 - U19
  • [9] Regulation of the INK4b-ARF-INK4a tumour suppressor locus:: all for one or one for all
    Gil, Jesus
    Peters, Gordon
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (09) : 667 - 677
  • [10] Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
    Gupta, Rajnish A.
    Shah, Nilay
    Wang, Kevin C.
    Kim, Jeewon
    Horlings, Hugo M.
    Wong, David J.
    Tsai, Miao-Chih
    Hung, Tiffany
    Argani, Pedram
    Rinn, John L.
    Wang, Yulei
    Brzoska, Pius
    Kong, Benjamin
    Li, Rui
    West, Robert B.
    van de Vijver, Marc J.
    Sukumar, Saraswati
    Chang, Howard Y.
    [J]. NATURE, 2010, 464 (7291) : 1071 - U148