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CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer

  • Research Article
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Tumor Biology

Abstract

The prognosis of non-small cell lung cancer (NSCLC) is still poor, and it is necessary to identify effectively diagnostic and prognostic biomarkers for NSCLC. Recent evidence demonstrates that long non-coding RNA (lncRNA) is actively transcribed from human genome. Some lncRNAs show a time- or tissue-specific expression manner and play important roles in diverse biological processes. Additionally, various cancer-associated lncRNAs have been identified, such as metastasis-associated lung adenocarcinoma transcript 1 for lung cancer. Here, we characterized the expression profile of a novel lncRNA, colon cancer-associated transcript 2 (CCAT2), in lung cancer and found that CCAT2 was significantly over-expressed in NSCLC tissues compared with paired adjacent normal tissues, with an average up-regulation fold of 7.5. Intriguingly, over-expression of CCAT2 was significantly associated with lung adenocarcinoma (p = 0.033) but not squamous cell cancer. Silencing CCAT2 by siRNA led to inhibition of proliferation and invasion in NSCLC cell lines in vitro. Additionally, CCAT2 combined with CEA could predict lymph node metastasis. Our findings indicate that CCAT2 is a lung adenocarcinoma-specific lncRNA and promotes invasion of NSCLC and highlight its potential as a biomarker for lymph node metastasis.

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References

  1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer. 1999;80(6):827–41.

    Article  CAS  PubMed  Google Scholar 

  2. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002;52(1):23–47.

    Article  PubMed  Google Scholar 

  3. Rosell R, Bivona TG, Karachaliou N. Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 2013;382(9893):720–31.

    Article  CAS  PubMed  Google Scholar 

  4. Yang X, Zhang Z, Qiu M, Hu J, Fan X, Wang J, et al. Glypican-5 Is a novel metastasis suppressor gene in non-small cell lung cancer. Cancer Lett. 2013;341(2):265–73.

    Article  CAS  PubMed  Google Scholar 

  5. Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1 % of the human genome by the Encode Pilot Project. Nature. 2007;447(7146):799–816.

    Article  CAS  PubMed  Google Scholar 

  6. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.

    Article  CAS  PubMed  Google Scholar 

  7. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136(4):642–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Takayama K, Horie-Inoue K, Katayama S, Suzuki T, Tsutsumi S, Ikeda K, et al. Androgen-responsive long noncoding RNA Ctbp1-as promotes prostate cancer. EMBO J. 2013;32(12):1665–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22(39):8031–41.

    Article  PubMed  Google Scholar 

  11. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73(3):1180–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132(1):330–42.

    Article  CAS  PubMed  Google Scholar 

  14. Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.

    Article  CAS  PubMed  Google Scholar 

  15. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50.

    Article  PubMed  Google Scholar 

  16. Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, et al. Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013. doi:10.1016/j.ejca.2013.04.026.

    Google Scholar 

  17. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol. 2011;6(12):1984–92.

    Article  PubMed  Google Scholar 

  18. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis RS, et al. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 2013;23(9):1446–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Redis RS, Sieuwerts AM, Look MP, Tudoran O, Ivan C, Spizzo R, et al. CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations. Oncotarget. 2013;4(10):1748–62.

    PubMed Central  PubMed  Google Scholar 

  20. Yin R, Zhang S, Wu Y, Fan X, Jiang F, Zhang Z, et al. Microrna-145 suppresses lung adenocarcinoma-initiating cell proliferation by targeting Oct4. Oncol Rep. 2011;25(6):1747–54.

    CAS  PubMed  Google Scholar 

  21. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.

    Article  CAS  PubMed  Google Scholar 

  22. Qiu MT, Hu JW, Yin R, Xu L. Long noncoding RNA: an emerging paradigm of cancer research. Tumour Biol. 2013;34(2):613–20.

    Article  CAS  PubMed  Google Scholar 

  23. Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, et al. Repression of the long noncoding RNA—let by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013. doi:10.1016/j.molcel.2013.01.010.

    Google Scholar 

  24. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A, Qu K, et al. Control of somatic tissue differentiation by the long non-coding RNA Tincr. Nature. 2013;493(7431):231–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Wu W, Bhagat TD, Yang X, Song JH, Cheng Y, Agarwal R, et al. Hypomethylation of noncoding DNA Regions and overexpression of the long noncoding RNA, Afap1–As1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013. doi:10.1053/j.gastro.2013.01.019.

    Google Scholar 

  26. Bertozzi D, Iurlaro R, Sordet O, Marinello J, Zaffaroni N, Capranico G. Characterization of novel antisense Hif-1alpha transcripts in human cancers. Cell Cycle. 2011;10(18):3189–97.

    Article  CAS  PubMed  Google Scholar 

  27. Guo F, Li Y, Liu Y, Wang J, Li G. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in Caski human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai). 2010;42(3):224–9.

    Article  CAS  Google Scholar 

  28. Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, et al. Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013;49(13):2949–59.

    Article  CAS  PubMed  Google Scholar 

  29. Haiman CA, Le Marchand L, Yamamato J, Stram DO, Sheng X, Kolonel LN, et al. A common genetic risk factor for colorectal and prostate cancer. Nat Genet. 2007;39(8):954–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, et al. A genome-wide association scan of tag Snps identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007;39(8):984–8.

    Article  CAS  PubMed  Google Scholar 

  31. Ghoussaini M, Song H, Koessler T, Al Olama AA, Kote-Jarai Z, Driver KE, et al. Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst. 2008;100(13):962–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Zhang X, Chen Q, He C, Mao W, Zhang L, Xu X, et al. Polymorphisms on 8q24 are associated with lung cancer risk and survival in Han Chinese. PLoS One. 2012;7(7):e41930.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Conflicts of interests

None

Funding sources

This study is funded by the Natural Science Foundation of China (81372321, 81201830), Natural Science Foundation for High Education of Jiangsu Province (13KJB320010), Research and Innovation Program for Graduates of Jiangsu Province (CXLX13_571), Human Resource Summit Grant of Jiangsu Province (10-D-078), and Key Clinical Medicine Technology Foundation of Jiangsu Province (BL2012030).

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Correspondence to Lin Xu or Rong Yin.

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Mantang Qiu and Youtao Xu are contributed equally to this work

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Qiu, M., Xu, Y., Yang, X. et al. CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer. Tumor Biol. 35, 5375–5380 (2014). https://doi.org/10.1007/s13277-014-1700-z

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  • DOI: https://doi.org/10.1007/s13277-014-1700-z

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