Proceedings of the National Academy of Sciences · 2014 · 184 citations · 23 references
MedicineGeneticsMolecular GeneticsCancer GeneticsGene ExpressionMolecular OncologyCancer GenomicsLong-range Gene RegulationMyc Family OncogenesNoncoding Rna BiologyNoncoding Rna FunctionNoncoding Rna In CancerCancer Susceptibility SyndromesCancer-related Noncoding Rna FunctionEnhancer RnasLong Noncoding Rna InteractionsLong Noncoding Rna RegulationNoncoding Rna-mediated Gene RegulationOncogenic Noncoding RnaPromoter-associated Noncoding Rnas
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.
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