Long-range interaction and correlation between <i>MYC</i> enhancer and oncogenic long noncoding RNA <i>CARLo-5</i>

Tae‐Wan Kim, Ri Cui(Yanbian University), Young-Jun Jeon(The Ohio State University), Ji Hoon Lee(University of California, Santa Cruz), Ju‐Hee Lee(University of California, Santa Cruz), Hosung Sim(University of Michigan), Jong Kook Park(Northwestern University), Paolo Fadda(The Ohio State University), Esmerina Tili(The Ohio State University Wexner Medical Center), Hiroshi Nakanishi(The Ohio State University), Man‐Il Huh(Kyungpook National University), Sung-Hak Kim(Korea University), Ju Hwan Cho(The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute), Bong Hwan Sung(Vanderbilt University Medical Center), Yong Peng(The Ohio State University), Tae Jin Lee(The Ohio State University), Zhenghua Luo(The Ohio State University), Hui-Lung Sun(The Ohio State University), Huijun Wei, Hansjüerg Alder(The Ohio State University), Jeong Su Oh(Sungkyunkwan University), Kang Sup Shim(The Ohio State University), Sang-Bong Ko(Daegu Catholic University), Carlo M. Croce(The Ohio State University)
Proceedings of the National Academy of Sciences
March 4, 2014
10.1073/pnas.1400350111
Cited by 184Open Access
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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.

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