Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma
- 2.1k Downloads
Long noncoding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are deregulated in many tumors. The specific aim of this study was to determine the role of a long noncoding RNA CCAT1 in the progression of gastric carcinoma and discover which factors contribute to the deregulation of CCAT1.
A computational screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with the CCAT1 promoter in vivo was tested by chromatin immunoprecipitation assay. CCAT1 promoter activities were examined by luciferase reporter assay. The function of the c-Myc binding site in the CCAT1 promoter region was tested by a promoter assay with nucleotide substitutions in the putative E-box. The effect of CCAT1 on gastric carcinoma cell proliferation and migration was tested using in vitro cell proliferation and migration assays.
CCAT1 levels were markedly increased in gastric carcinoma tissues compared with normal tissues. c-Myc directly binds to the E-box element in the promoter region of CCAT1, and when ectopically expressed increased promoter activity and expression of CCAT1. Nucleotide substitutions in the E-box element in the promoter region abrogated c-Myc-dependent promoter activation. The expression of CCAT1 and c-Myc shows strong association in gastric carcinomas. Moreover, abnormally expressed CCAT1 promotes cell proliferation and migration.
These data suggest that c-Myc induction of CCAT1 holds an important role in gastric carcinoma and implicate the potential application of CCAT1 in the treatment of gastric carcinoma.
KeywordsLong noncoding RNA CCAT1 c-Myc Gastric carcinoma
Conflict of interest
The authors have declared that no competing interest exists.
- Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076PubMedCrossRefGoogle Scholar
- Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142(3):409–419PubMedCrossRefGoogle Scholar
- Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, Horlings HM, Shah N, Umbricht C, Wang P, Kong B, Langerod A, Borresen-Dale AL, Kim SK, van de Vijver M, Sukumar S, Whitfield ML, Kellis M, Xiong Y, Wong DJ, Chang HY (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet 43(7):621–629PubMedCrossRefGoogle Scholar
- Nissan A, Stojadinovic A, Mitrani-Rosenbaum S, Halle D, Grinbaum R, Roistacher M, Bochem A, Dayanc BE, Ritter G, Gomceli I, Bostanci EB, Akoglu M, Chen YT, Old LJ, Gure AO (2012) Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues. Int J Cancer 130(7):1598–1606PubMedCrossRefGoogle Scholar
- Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, Zatloukal K (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132(1):330–342PubMedCrossRefGoogle Scholar
- Spizzo R, Almeida MI, Colombatti A, Calin GA (2012) Long non-coding RNAs and cancer: a new frontier of translational research? OncogeneGoogle Scholar
- Yan B, Wang Z (2012) Long Noncoding RNA: Its Physiological and Pathological Roles. DNA Cell Biol. doi: 10.1089/dna.2011.1544
- Zhu Y, Xiao X, Dong L, Liu Z (2012) Investigation and identification of let-7a related functional proteins in gastric carcinoma by proteomics. Anal Cell Pathol (Amst) 35(4):285–295Google Scholar