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A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival

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Tumor Biology

Abstract

Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two major histological types of non-small cell lung cancer. LSCC differs greatly from LAD in many aspects. Accumulating evidence has shown that long noncoding RNA (lncRNA) plays an important role in the process of carcinogenesis and tumor progression. Expression of lncRNA is highly tissue-specific and could be biomarkers for cancer diagnosis and prognosis. Here, we identified differentially expressed lncRNA between LSCC and LAD by data mining of Affymetrix HG-U133 Plus 2.0 microarray. A set of 1646 differentially expressed lncRNA transcripts were identified. Among these lncRNAs, a novel lncRNA, LINC01133, showed the largest fold change among large intergenic noncoding RNAs. Quantitative real-time polymerase chain reaction (PCR) assay confirmed that LINC01133 was upregulated in LSCC (increasing fold 6.4, P < 0.01) but not in the LAD samples. LSCC patients with higher expression level of LINC01133 had shorter survival time (hazard ratio = 2.383; 95 % confidence interval 1.023–5.547, P = 0.044). Wound-healing and transwell assays demonstrated that silence of LINC01133 by small interfering RNA (siRNA) inhibited invasion ability of LSCC cell line. Thus, a set of lncRNA was differentially expressed between LAD and LSCC and could serve as potential biomarkers.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.

    Article  PubMed  Google Scholar 

  2. 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 

  3. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.

    Article  PubMed  Google Scholar 

  4. Yildiz O, Buyuktas D, Ekiz E, Selcukbiricik F, Papila I, Papila C. Facial nerve palsy: an unusual presenting feature of small cell lung cancer. Case Rep Oncol. 2011;4(1):35–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease. Nat Rev Cancer. 2007;7(10):778–90.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Consortium EP, Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, 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  Google Scholar 

  9. Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47(3):199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Prensner JR, Zhao S, Erho N, Schipper M, Iyer MK, Dhanasekaran SM, et al. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol. 2014;15(13):1469–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Garzon R, Volinia S, Papaioannou D, Nicolet D, Kohlschmidt J, Yan PS, et al. Expression and prognostic impact of lncRNAs in acute myeloid leukemia. Proc Natl Acad Sci U S A. 2014;111(52):18679–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71(1):3–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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 

  14. Sanchez Y, Segura V, Marin-Bejar O, Athie A, Marchese FP, Gonzalez J, et al. Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature. Nat Commun. 2014;5:5812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ding X, Zhu L, Ji T, Zhang X, Wang F, Gan S, et al. Long intergenic non-coding RNAs (lincRNAs) identified by RNA-seq in breast cancer. PLoS One. 2014;9(8):e103270.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ren S, Peng Z, Mao JH, Yu Y, Yin C, Gao X, et al. RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res. 2012;22(5):806–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang P, Lu S, Mao H, Bai Y, Ma T, Cheng Z, et al. Identification of biomarkers for the detection of early stage lung adenocarcinoma by microarray profiling of long noncoding RNAs. Lung Cancer. 2015.

  18. Xue Y, Ma G, Zhang Z, Hua Q, Chu H, Tong N, et al. A novel antisense long noncoding RNA regulates the expression of MDC1 in bladder cancer. Oncotarget. 2015;6(1):484–93.

    PubMed  Google Scholar 

  19. 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;49(6):1083–96.

    Article  CAS  PubMed  Google Scholar 

  20. Kuner R, Muley T, Meister M, Ruschhaupt M, Buness A, Xu EC, et al. Global gene expression analysis reveals specific patterns of cell junctions in non-small cell lung cancer subtypes. Lung Cancer. 2009;63(1):32–8.

    Article  PubMed  Google Scholar 

  21. Bonnefont J, Laforge T, Plastre O, Beck B, Sorce S, Dehay C, et al. Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation. Cell Death Differ. 2011;18(2):293–303.

    Article  CAS  PubMed  Google Scholar 

  22. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249–64.

    Article  PubMed  Google Scholar 

  23. Smyth GK. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:Article3.

  24. Yang J, Lin J, Liu T, Chen T, Pan S, Huang W, et al. Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. Lung Cancer. 2014;85(2):110–5.

    Article  PubMed  Google Scholar 

  25. Zhang X, Sun S, Pu JK, Tsang AC, Lee D, Man VO, et al. Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis. 2012;48(1):1–8.

    Article  PubMed  Google Scholar 

  26. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol. 2011;29(8):742–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xu G, Chen J, Pan Q, Huang K, Pan J, Zhang W, et al. Long noncoding RNA expression profiles of lung adenocarcinoma ascertained by microarray analysis. PLoS One. 2014;9(8):e104044.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Giordano TJ, Kuick R, Else T, Gauger PG, Vinco M, Bauersfeld J, et al. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009;15(2):668–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, et al. Human cancer long non-coding RNA transcriptomes. PLoS One. 2011;6(10):e25915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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  CAS  PubMed  Google Scholar 

  32. 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;144(5):956–66 e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Disease, Huashan Hospital, Fudan University, No. 12 Wulumuqi Middle Road, Shanghai, 200040, China

    Jing Zhang, Ning Zhu & Xiaodong Chen

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  1. Jing Zhang
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  2. Ning Zhu
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  3. Xiaodong Chen
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Correspondence to Xiaodong Chen.

Additional information

Jing Zhang and Ning Zhu contributed equally to this work.

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Supplementary Table 1

Differentially expressed lncRNAs between LSCC and LAD (XLSX 187 kb)

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Zhang, J., Zhu, N. & Chen, X. A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival. Tumor Biol. 36, 7465–7471 (2015). https://doi.org/10.1007/s13277-015-3460-9

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  • DOI: https://doi.org/10.1007/s13277-015-3460-9

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