Human Colorectal Cancer-specific CCAT1-L LncRNA Regulates Long-range Chromatin Interactions at the MYC Locus

Overview

Journal Cell Res

Specialty Cell Biology

Date 2014 Mar 26

PMID 24662484

Citations 416

Authors

Jian-Feng Xiang

Qing-Fei Yin

Tian Chen

Yang Zhang

Xiao-Ou Zhang

Zheng Wu

Shaofeng Zhang

Hai-Bin Wang

Junhui Ge

Xuhua Lu

Li Yang

Ling-Ling Chen

Affiliations

Soon will be listed here.

Abstract

The human 8q24 gene desert contains multiple enhancers that form tissue-specific long-range chromatin loops with the MYC oncogene, but how chromatin looping at the MYC locus is regulated remains poorly understood. Here we demonstrate that a long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role in MYC transcriptional regulation and promotes long-range chromatin looping. Importantly, the CCAT1-L locus is located within a strong super-enhancer and is spatially close to MYC. Knockdown of CCAT1-L reduced long-range interactions between the MYC promoter and its enhancers. In addition, CCAT1-L interacts with CTCF and modulates chromatin conformation at these loop regions. These results reveal an important role of a previously unannotated lncRNA in gene regulation at the MYC locus.

Citing Articles

The LncRNA lnc-POTEM-4:14 promotes HCC progression by interacting with FOXK1.

Peng B, Quan Z, Liang L, Liu M, Hu K, Chen S Sci Rep. 2025; 15(1):7672.

PMID: 40044876 PMC: 11882843. DOI: 10.1038/s41598-025-92614-4.

Understanding lncRNAs: key regulators of myogenesis and lipogenesis in farm animals.

Liu W, Chen M, Liu Y, Li X, Li H, Wang J Front Vet Sci. 2025; 12:1540613.

PMID: 40027357 PMC: 11868070. DOI: 10.3389/fvets.2025.1540613.

Non-Coding RNAs in Cancer: Structure, Function, and Clinical Application.

Marton E, Varga A, Domoszlai D, Buglyo G, Balazs A, Penyige A Cancers (Basel). 2025; 17(4).

PMID: 40002172 PMC: 11853212. DOI: 10.3390/cancers17040579.

Comprehensive dissection of cis-regulatory elements in a 2.8 Mb topologically associated domain in six human cancers.

Caragine C, Le V, Mustafa M, Diaz B, Morris J, Muller S Nat Commun. 2025; 16(1):1611.

PMID: 39948336 PMC: 11825950. DOI: 10.1038/s41467-025-56568-5.

Diagnostics and Therapy for Malignant Tumors.

Tsai C, Wang C, Chang H, Chang P, Chang C, Chu T Biomedicines. 2025; 12(12.

PMID: 39767566 PMC: 11726849. DOI: 10.3390/biomedicines12122659.

References

Bulger M, Groudine M . Functional and mechanistic diversity of distal transcription enhancers. Cell. 2011; 144(3):327-39. PMC: 3742076. DOI: 10.1016/j.cell.2011.01.024. View

Phillips J, Corces V . CTCF: master weaver of the genome. Cell. 2009; 137(7):1194-211. PMC: 3040116. DOI: 10.1016/j.cell.2009.06.001. View

Huarte M, Guttman M, Feldser D, Garber M, Koziol M, Kenzelmann-Broz D . A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010; 142(3):409-19. PMC: 2956184. DOI: 10.1016/j.cell.2010.06.040. View

Herold M, Bartkuhn M, Renkawitz R . CTCF: insights into insulator function during development. Development. 2012; 139(6):1045-57. DOI: 10.1242/dev.065268. View

Gupta R, Shah N, Wang K, Kim J, Horlings H, Wong D . Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010; 464(7291):1071-6. PMC: 3049919. DOI: 10.1038/nature08975. View

Levens D . How the c-myc promoter works and why it sometimes does not. J Natl Cancer Inst Monogr. 2008; (39):41-3. PMC: 2683261. DOI: 10.1093/jncimonographs/lgn004. View

Yao H, Brick K, Evrard Y, Xiao T, Camerini-Otero R, Felsenfeld G . Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA. Genes Dev. 2010; 24(22):2543-55. PMC: 2975930. DOI: 10.1101/gad.1967810. View

Rinn J, Chang H . Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012; 81:145-66. PMC: 3858397. DOI: 10.1146/annurev-biochem-051410-092902. View

Lam M, Cho H, Lesch H, Gosselin D, Heinz S, Tanaka-Oishi Y . Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature. 2013; 498(7455):511-5. PMC: 3839578. DOI: 10.1038/nature12209. View

10.

Kawai K, Viars C, Arden K, Tarin D, Urquidi V, Goodison S . Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line. Genes Chromosomes Cancer. 2002; 34(1):1-8. DOI: 10.1002/gcc.10003. View

11.

Maston G, Evans S, Green M . Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006; 7:29-59. DOI: 10.1146/annurev.genom.7.080505.115623. View

12.

Tsai M, Manor O, Wan Y, Mosammaparast N, Wang J, Lan F . Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010; 329(5992):689-93. PMC: 2967777. DOI: 10.1126/science.1192002. View

13.

Burdach J, OConnell M, Mackay J, Crossley M . Two-timing zinc finger transcription factors liaising with RNA. Trends Biochem Sci. 2012; 37(5):199-205. DOI: 10.1016/j.tibs.2012.02.001. View

14.

Ong C, Corces V . Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet. 2011; 12(4):283-93. PMC: 3175006. DOI: 10.1038/nrg2957. View

15.

Gutschner T, Baas M, Diederichs S . Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases. Genome Res. 2011; 21(11):1944-54. PMC: 3205578. DOI: 10.1101/gr.122358.111. View

16.

Ulitsky I, Bartel D . lincRNAs: genomics, evolution, and mechanisms. Cell. 2013; 154(1):26-46. PMC: 3924787. DOI: 10.1016/j.cell.2013.06.020. View

17.

Hah N, Murakami S, Nagari A, Danko C, Kraus W . Enhancer transcripts mark active estrogen receptor binding sites. Genome Res. 2013; 23(8):1210-23. PMC: 3730096. DOI: 10.1101/gr.152306.112. View

18.

Stadhouders R, Kolovos P, Brouwer R, Zuin J, van den Heuvel A, Kockx C . Multiplexed chromosome conformation capture sequencing for rapid genome-scale high-resolution detection of long-range chromatin interactions. Nat Protoc. 2013; 8(3):509-24. DOI: 10.1038/nprot.2013.018. View

19.

Orom U, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G . Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010; 143(1):46-58. PMC: 4108080. DOI: 10.1016/j.cell.2010.09.001. View

20.

Kam Y, Rubinstein A, Naik S, Djavsarov I, Halle D, Ariel I . Detection of a long non-coding RNA (CCAT1) in living cells and human adenocarcinoma of colon tissues using FIT-PNA molecular beacons. Cancer Lett. 2013; 352(1):90-6. DOI: 10.1016/j.canlet.2013.02.014. View