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Erschienen in: Journal of Cancer Research and Clinical Oncology 3/2013

01.03.2013 | Original Paper

Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma

verfasst von: Feng Yang, Xuchao Xue, Jianwei Bi, Luming Zheng, Kangkang Zhi, Yan Gu, Guoen Fang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2013

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
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Literatur
Zurück zum Zitat Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS, Penn LZ (2006) The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 66(10):5330–5337PubMedCrossRef Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS, Penn LZ (2006) The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 66(10):5330–5337PubMedCrossRef
Zurück zum Zitat Calcagno DQ, Leal MF, Assumpcao PP, Smith MA, Burbano RR (2008) MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 14(39):5962–5968PubMedCrossRef Calcagno DQ, Leal MF, Assumpcao PP, Smith MA, Burbano RR (2008) MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol 14(39):5962–5968PubMedCrossRef
Zurück zum Zitat Calcagno DQ, Leal MF, Demachki S, Araujo MT, Freitas FW, Oliveira e Souza D, Assumpcao PP, Ishak G, de Arruda Cardoso Smith M, Burbano RR (2010) MYC in gastric carcinoma and intestinal metaplasia of young adults. Cancer Genet Cytogenet 202(1):63–66PubMedCrossRef Calcagno DQ, Leal MF, Demachki S, Araujo MT, Freitas FW, Oliveira e Souza D, Assumpcao PP, Ishak G, de Arruda Cardoso Smith M, Burbano RR (2010) MYC in gastric carcinoma and intestinal metaplasia of young adults. Cancer Genet Cytogenet 202(1):63–66PubMedCrossRef
Zurück zum Zitat Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F (2006) The c-Myc target gene network. Semin Cancer Biol 16(4):253–264PubMedCrossRef Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F (2006) The c-Myc target gene network. Semin Cancer Biol 16(4):253–264PubMedCrossRef
Zurück zum Zitat 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):1071–1076PubMedCrossRef 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):1071–1076PubMedCrossRef
Zurück zum Zitat Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374(9688):477–490PubMedCrossRef Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374(9688):477–490PubMedCrossRef
Zurück zum Zitat 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):409–419PubMedCrossRef 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):409–419PubMedCrossRef
Zurück zum Zitat 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):621–629PubMedCrossRef 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):621–629PubMedCrossRef
Zurück zum Zitat Krzyzanowski PM, Muro EM, Andrade-Navarro MA (2012) Computational approaches to discovering noncoding RNA. Wiley Interdiscip Rev RNA 3(4):567–579PubMedCrossRef Krzyzanowski PM, Muro EM, Andrade-Navarro MA (2012) Computational approaches to discovering noncoding RNA. Wiley Interdiscip Rev RNA 3(4):567–579PubMedCrossRef
Zurück zum Zitat Li L, Feng T, Lian Y, Zhang G, Garen A, Song X (2009) Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci USA 106(31):12956–12961PubMedCrossRef Li L, Feng T, Lian Y, Zhang G, Garen A, Song X (2009) Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci USA 106(31):12956–12961PubMedCrossRef
Zurück zum Zitat Milne AN, Carneiro F, O’Morain C, Offerhaus GJ (2009) Nature meets nurture: molecular genetics of gastric cancer. Hum Genet 126(5):615–628PubMedCrossRef Milne AN, Carneiro F, O’Morain C, Offerhaus GJ (2009) Nature meets nurture: molecular genetics of gastric cancer. Hum Genet 126(5):615–628PubMedCrossRef
Zurück zum Zitat Moore MA, Attasara P, Khuhaprema T, Le TN, Nguyen TH, Raingsey PP, Sriamporn S, Sriplung H, Srivanatanakul P, Bui DT, Wiangnon S, Sobue T (2010) Cancer epidemiology in mainland South-East Asia—past, present and future. Asian Pac J Cancer Prev 11(Suppl 2):67–80PubMed Moore MA, Attasara P, Khuhaprema T, Le TN, Nguyen TH, Raingsey PP, Sriamporn S, Sriplung H, Srivanatanakul P, Bui DT, Wiangnon S, Sobue T (2010) Cancer epidemiology in mainland South-East Asia—past, present and future. Asian Pac J Cancer Prev 11(Suppl 2):67–80PubMed
Zurück zum Zitat Moran VA, Perera RJ, Khalil AM (2012) Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 40(14):6391–6400PubMedCrossRef Moran VA, Perera RJ, Khalil AM (2012) Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 40(14):6391–6400PubMedCrossRef
Zurück zum Zitat 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):1598–1606PubMedCrossRef 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):1598–1606PubMedCrossRef
Zurück zum Zitat Nobili S, Bruno L, Landini I, Napoli C, Bechi P, Tonelli F, Rubio CA, Mini E, Nesi G (2011) Genomic and genetic alterations influence the progression of gastric cancer. World J Gastroenterol 17(3):290–299PubMedCrossRef Nobili S, Bruno L, Landini I, Napoli C, Bechi P, Tonelli F, Rubio CA, Mini E, Nesi G (2011) Genomic and genetic alterations influence the progression of gastric cancer. World J Gastroenterol 17(3):290–299PubMedCrossRef
Zurück zum Zitat Oster SK, Ho CS, Soucie EL, Penn LZ (2002) The myc oncogene: marvelouslY complex. Adv Cancer Res 84:81–154PubMedCrossRef Oster SK, Ho CS, Soucie EL, Penn LZ (2002) The myc oncogene: marvelouslY complex. Adv Cancer Res 84:81–154PubMedCrossRef
Zurück zum Zitat 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):330–342PubMedCrossRef 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):330–342PubMedCrossRef
Zurück zum Zitat Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641PubMedCrossRef Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641PubMedCrossRef
Zurück zum Zitat Solomon DL, Amati B, Land H (1993) Distinct DNA binding preferences for the c-Myc/Max and Max/Max dimers. Nucleic Acids Res 21(23):5372–5376PubMedCrossRef Solomon DL, Amati B, Land H (1993) Distinct DNA binding preferences for the c-Myc/Max and Max/Max dimers. Nucleic Acids Res 21(23):5372–5376PubMedCrossRef
Zurück zum Zitat Song L, Dai T, Xie Y, Wang C, Lin C, Wu Z, Ying Z, Wu J, Li M, Li J (2012) Up-regulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair. J Mol Cell Biol 4(2):108–117PubMedCrossRef Song L, Dai T, Xie Y, Wang C, Lin C, Wu Z, Ying Z, Wu J, Li M, Li J (2012) Up-regulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair. J Mol Cell Biol 4(2):108–117PubMedCrossRef
Zurück zum Zitat Spizzo R, Almeida MI, Colombatti A, Calin GA (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene Spizzo R, Almeida MI, Colombatti A, Calin GA (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene
Zurück zum Zitat Tsai MC, Spitale RC, Chang HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71(1):3–7PubMedCrossRef Tsai MC, Spitale RC, Chang HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71(1):3–7PubMedCrossRef
Zurück zum Zitat Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914PubMedCrossRef Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914PubMedCrossRef
Zurück zum Zitat Zhang L, Hou Y, Ashktorab H, Gao L, Xu Y, Wu K, Zhai J (2010) The impact of C-MYC gene expression on gastric cancer cell. Mol Cell Biochem 344(1–2):125–135PubMedCrossRef Zhang L, Hou Y, Ashktorab H, Gao L, Xu Y, Wu K, Zhai J (2010) The impact of C-MYC gene expression on gastric cancer cell. Mol Cell Biochem 344(1–2):125–135PubMedCrossRef
Zurück zum Zitat 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):285–295 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):285–295
Metadaten
Titel
Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma
verfasst von
Feng Yang
Xuchao Xue
Jianwei Bi
Luming Zheng
Kangkang Zhi
Yan Gu
Guoen Fang
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-012-1324-x

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