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

Kim T, Cui R, Jeon YJ, Lee JH, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, Huh MI, Kim SH, Cho JH, Sung BH, Peng Y, Lee TJ, Luo Z, Sun HL, Wei H, Alder H, Oh JS, Shim KS, Ko SB, Croce CM
Proc Natl Acad Sci U S A. 2014 111 (11): 4173-8

PMID: 24594601 · PMCID: PMC3964128 · DOI:10.1073/pnas.1400350111

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 (16)

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

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