Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5

Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4173-8. doi: 10.1073/pnas.1400350111. Epub 2014 Mar 4.

Abstract

The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here we report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, we demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, our data provide a key of the mystery of the 8q24 gene desert.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 8 / genetics*
  • Enhancer Elements, Genetic / genetics
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering

Associated data

  • GENBANK/JX003864
  • GENBANK/JX003865
  • GENBANK/JX003866
  • GENBANK/JX003867
  • GENBANK/JX003868
  • GENBANK/JX003869
  • GENBANK/JX003870
  • GENBANK/JX003871
  • GENBANK/JX003872
  • GENBANK/JX003873
  • GENBANK/JX003874
  • GEO/GSE48877