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

2014; National Academy of Sciences; Volume: 111; Issue: 11 Linguagem: Inglês

10.1073/pnas.1400350111

1091-6490

Tae‐Wan Kim, Ri Cui, Young-Jun Jeon, Ji Hoon Lee, Ju‐Hee Lee, Hosung Sim, Jong Kook Park, Paolo Fadda, Esmerina Tili, Hiroshi Nakanishi, Man-Il Huh, Sung-Hak Kim, Ju Hwan Cho, Bong Hwan Sung, Yong Peng, Tae Jin Lee, Zhenghua Luo, Hui-Lung Sun, Huijun Wei, Hansjüerg Alder, Jeong Su Oh, Kang Sup Shim, Sang-Bong Ko, Carlo M. Croce,

RNA modifications and cancer

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.