Tumor Biology

, Volume 37, Issue 3, pp 3683–3695 | Cite as

An integrative transcriptomic analysis reveals p53 regulated miRNA, mRNA, and lncRNA networks in nasopharyngeal carcinoma

  • Zhaojian Gong
  • Qian Yang
  • Zhaoyang Zeng
  • Wenling Zhang
  • Xiayu Li
  • Xuyu Zu
  • Hao Deng
  • Pan Chen
  • Qianjin Liao
  • Bo Xiang
  • Ming Zhou
  • Xiaoling Li
  • Yong Li
  • Wei Xiong
  • Guiyuan Li
Original Article


It has been reported that p53 dysfunction is closely related to the carcinogenesis of nasopharyngeal carcinoma (NPC). Recently, an increasing body of evidence has indicated that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) participate in p53-associated signaling pathways and, in addition to mRNAs, form a complex regulation network to promote tumor occurrence and progression. The aim of this study was to elucidate the p53-regulated miRNAs, mRNAs, and lncRNAs and their regulating networks in NPC. Firstly, we overexpressed p53 in the NPC cell line HNE2 and performed transcriptomic gene expression profiling (GEP) analysis, which included miRNAs, mRNAs, and lncRNAs, using microarray technology at 0, 12, 24, and 48 h after transfection. There were 38 miRNAs (33 upregulated and 5 downregulated), 2107 mRNAs (296 upregulated and 1811 downregulated), and 1190 lncRNAs (133 upregulated and 1057 downregulated) that were significantly dysregulated by p53. Some of the dysregulated molecules were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Then, we integrated previously published miRNAs, mRNAs, and lncRNAs GEP datasets from NPC biopsies to investigate the expression of these p53 regulated molecules and found that 7 miRNAs, 218 mRNAs, and 101 lncRNAs regulated by p53 were also differentially expressed in NPC tissues. Finally, p53-regulated miRNA, mRNA, and lncRNA networks were constructed using bioinformatics methods. These miRNAs, mRNAs, and lncRNAs may participate in p53 downstream signaling pathways and play important roles in the carcinogenesis of NPC. Thorough investigations of their biological functions and regulating relationships will provide a novel view of the p53 signaling pathway, and the restoration of p53 functioning or its downstream gene regulating network is potentially of great value in treating NPC patients.


p53 Nasopharyngeal carcinoma (NPC) microRNAs (miRNAs) mRNAs Long noncoding RNAs (lncRNAs) Gene regulating network 



This study was supported in part by grants from the National Natural Science Foundation of China (81172189, 81272298, 81372907, 81301757, 81472531, 81402009, 81572787, and 81528019) and the Natural Science Foundation of Hunan Province (14JJ1010 and 2015JJ1022).

Compliance with ethical standards

Conflicts of interest


Supplementary material

13277_2015_4156_Fig8_ESM.gif (134 kb)
Supplemental Figure S1

The expression of p53 was validated in HNE2 cells after transfection with TP53 gene plasmid. Real-time-PCR (a) and western blotting (b) were used to detect the mRNA and protein expression levels of p53 in HNE2 cells after transfection with TP53 gene plasmid, respectively. GAPDH was used as the control. (c) The p53 overexpression plasmid pCMV-p53 and luciferase reporter plasmid containing p53 binding sites used for assaying p53 transcriptional activity, the pp53-TA-luc, were cotransfected into HNE2 cells, and transcriptional activity of p53 from 0–48 h post-transfection was determined by luciferase assays. (GIF 42 kb) (GIF 134 kb)

13277_2015_4156_MOESM1_ESM.tif (2.4 mb)
(TIFF 2451 kb)
13277_2015_4156_Fig9_ESM.gif (235 kb)
Supplemental Figure S2

Networks of TP53-regulated genes in NPC cell line HNE2. Ingenuity Pathway Analysis software (IPA) was used to analyze p53 target genes. Four networks were identified. The main network is shown in Fig. 2c. The intensity of a node color indicates the degree of up-regulation (red). The meanings of the node shapes are indicated in the figure. (GIF 235 kb)

13277_2015_4156_MOESM2_ESM.tif (4.6 mb)
(TIFF 4661 kb)
13277_2015_4156_Fig10_ESM.gif (43 kb)
Supplemental Figure S3

Real-time PCR confirms the differentially expressed mRNA regulated by p53 in HNE2 cells. The expression levels of CDKN1A (a) and MDM2 (b) were confirmed in HNE2. The expression level of mRNAs at 0 h after TP53 transfection was used as the control and was normalized. The data are shown as the means of three independent experiments. *. P < 0.05; **, p < 0.01; ***, p < 0.001. (GIF 42 kb)

13277_2015_4156_MOESM3_ESM.tif (602 kb)
(TIFF 601 kb)
13277_2015_4156_Fig11_ESM.gif (350 kb)
Supplemental Figure S4

Construction of the miRNAs and their targeted mRNAs networks regulated by p53 through IPA software. Thirty-three up-regulated miRNAs and 1911 down-regulated mRNAs, as well as 5 down-regulated miRNAs and 296 up-regulated mRNAs, identified in p53 transfected HNE2 cells were entered into IPA software, and 2534 potential miRNAs-mRNAs pairs were identified among these differentially expressed miRNAs and mRNAs through the miRNA target screening strategy. The miRNA-mRNA interaction network was constructed by Cytoscape software. (GIF 349 kb)

13277_2015_4156_MOESM4_ESM.tif (5.8 mb)
(TIFF 5936 kb)
13277_2015_4156_MOESM5_ESM.xls (26 kb)
Supplemental Table S1 The differentially expressed miRNAs in HNE2 cells after 0, 12, 24, and 48 h of transfection with the p53 expression vector pCMV-p53. (XLS 25 kb)
13277_2015_4156_MOESM6_ESM.xls (333 kb)
Supplemental Table S2 The differentially expressed mRNAs in HNE2 cells after 0, 12, 24, and 48 h of transfection with the p53 expression vector pCMV-p53 . (XLS 333 kb)
13277_2015_4156_MOESM7_ESM.xls (197 kb)
Supplemental Table S3 The differentially expressed lncRNAs in HNE2 cells after 0, 12, 24, and 48 h of transfection with the p53 expression vector pCMV-p53. (XLS 197 kb)


  1. 1.
    Zeng Z, Huang H, Zhang W, Xiang B, Zhou M, et al. Nasopharyngeal carcinoma: advances in genomics and molecular genetics. Sci China Life Sci. 2011;54:966–75.CrossRefPubMedGoogle Scholar
  2. 2.
    Xiong W, Zeng ZY, Xia JH, Xia K, Shen SR, et al. A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res. 2004;64:1972–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Zeng Z, Zhou Y, Zhang W, Li X, Xiong W, et al. Family-based association analysis validates chromosome 3p21 as a putative nasopharyngeal carcinoma susceptibility locus. Genet Med. 2006;8:156–60.CrossRefPubMedGoogle Scholar
  4. 4.
    Stoker SD, van Diessen JN, de Boer JP, Karakullukcu B, Leemans CR, et al. Current treatment options for local residual nasopharyngeal carcinoma. Curr Treat Options Oncol. 2013;14:475–91.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Liao Q, Zeng Z, Guo X, Li X, Wei F, et al. LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation. Oncogene. 2014;33:2098–109.CrossRefPubMedGoogle Scholar
  6. 6.
    Yang Y, Liao Q, Wei F, Li X, Zhang W, et al. LPLUNC1 inhibits nasopharyngeal carcinoma cell growth via down-regulation of the MAP kinase and cyclin D1/E2F pathways. PLoS One. 2013;8, e62869.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zeng Z, Zhou Y, Xiong W, Luo X, Zhang W, et al. Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray. J Cancer Res Clin Oncol. 2007;133:71–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Zeng ZY, Zhou YH, Zhang WL, Xiong W, Fan SQ, et al. Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally regulated Wnt signaling pathway. Hum Pathol. 2007;38:120–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang W, Fan S, Zou G, Shi L, Zeng Z, et al. Lactotransferrin could be a novel independent molecular prognosticator of nasopharyngeal carcinoma. Tumour Biol. 2015;36:675–83.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang W, Zeng Z, Zhou Y, Xiong W, Fan S, et al. Identification of aberrant cell cycle regulation in Epstein-Barr virus-associated nasopharyngeal carcinoma by cDNA microarray and gene set enrichment analysis. Acta Biochim Biophys Sin (Shanghai). 2009;41:414–28.CrossRefGoogle Scholar
  11. 11.
    Zhang W, Zeng Z, Fan S, Wang J, Yang J, et al. Evaluation of the prognostic value of TGF-beta superfamily type I receptor and TGF-beta type II receptor expression in nasopharyngeal carcinoma using high-throughput tissue microarrays. J Mol Histol. 2012;43:297–306.CrossRefPubMedGoogle Scholar
  12. 12.
    Huang HB, Deng M, Zheng Y, Zhou YH, Zhang WL, et al. Innate immune protein lactotransferrin prevents initiation and arrests progression of nasopharyngeal carcinoma. Prog Biochem Biophys. 2013;40:319–24.Google Scholar
  13. 13.
    Zeng Z, Fan S, Zhang X, Li S, Zhou M, et al. Epstein-Barr virus-encoded small RNA 1 (EBER-1) could predict good prognosis in nasopharyngeal carcinoma. Clin Transl Oncol. 2015;Google Scholar
  14. 14.
    Xiong W, Wu X, Starnes S, Johnson SK, Haessler J, et al. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood. 2008;112:4235–46.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gong ZJ, Huang HB, Xu K, Liang F, Li XL, et al. Advances in microRNAs and TP53 gene regulatory network. Prog Biochem Biophys. 2012;39:1133–44.CrossRefGoogle Scholar
  16. 16.
    Li Y, Gordon MW, Xu-Monette ZY, Visco C, Tzankov A, et al. Single nucleotide variation in the TP53 3′ untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121:4529–40.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gong Z, Zhang S, Zeng Z, Wu H, Yang Q, et al. LOC401317, a p53-regulated long non-coding RNA, inhibits cell proliferation and induces apoptosis in the nasopharyngeal carcinoma cell line HNE2. PLoS One. 2014;9, e110674.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Siomi H, Siomi MC. Posttranscriptional regulation of microRNA biogenesis in animals. Mol Cell. 2010;38:323–32.CrossRefPubMedGoogle Scholar
  20. 20.
    Rybak A, Fuchs H, Hadian K, Smirnova L, Wulczyn EA, et al. The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2. Nat Cell Biol. 2009;11:1411–20.CrossRefPubMedGoogle Scholar
  21. 21.
    Fan YY, Long B, Liu F, Zhou LY, Wang K, et al. Establishment of cardiomyocyte-specific miR-30b transgenic mice and exploring the function of miR-30b. Prog Biochem Biophys. 2014;41:575–82.Google Scholar
  22. 22.
    Pan YQ, Pan B, Liu XY, Li RZ, Yue JM. Dicer and its miRNAs are necessary gene and regulatory factors for differentiation and proliferation of vascular smooth muscle cell. Prog Biochem Biophys. 2014;41:1255–64.Google Scholar
  23. 23.
    Wu G, Wang D, Huang Y, Han JD. The research progress of microRNAs in aging. Prog Biochem Biophys. 2014;41:273–87.Google Scholar
  24. 24.
    Becker LE, Lu Z, Chen W, Xiong W, Kong M, et al. A systematic screen reveals microRNA clusters that significantly regulate four major signaling pathways. PLoS One. 2012;7, e48474.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ma X, Kumar M, Choudhury SN, Becker Buscaglia LE, Barker JR, et al. Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis. Proc Natl Acad Sci U S A. 2011;108:10144–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ma X, Conklin DJ, Li F, Dai Z, Hua X, et al. The oncogenic microRNA miR-21 promotes regulated necrosis in mice. Nat Commun. 2015;6:7151.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bo H, Gong Z, Zhang W, Li X, Zeng Y, et al. Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma. Oncotarget. 2015;6(24):20404–18.Google Scholar
  28. 28.
    Gong Z, Zhang S, Zhang W, Huang H, Li Q, et al. Long non-coding RNAs in cancer. Sci China Life Sci. 2012;55:1120–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Tang K, Wei F, Bo H, Huang HB, Zhang WL, et al. Cloning and functional characterization of a novel long non-coding RNA gene associated with hepatocellular carcinoma. Prog Biochem Biophys. 2014;41:153–62.Google Scholar
  30. 30.
    Zhang W, Huang C, Gong Z, Zhao Y, Tang K, et al. Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma. J Mol Histol. 2013;44:545–54.CrossRefPubMedGoogle Scholar
  31. 31.
    Li YW, Wang YM, Zhang XY, Xue D, Kuang B, et al. Progress of long noncoding RNA HOTAIR in human cancer. Prog Biochem Biophys. 2015;42:228–35.Google Scholar
  32. 32.
    Bu D, Luo H, Jiao F, Fang S, Tan C, et al. Evolutionary annotation of conserved long non-coding RNAs in major mammalian species. Sci China Life Sci. 2015;Google Scholar
  33. 33.
    Li J, Gao C, Wang Y, Ma W, Tu J, et al. A bioinformatics method for predicting long noncoding RNAs associated with vascular disease. Sci China Life Sci. 2014;57:852–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Chen YN, Xiong XD. Long noncoding RNA and epigenetic regulation. Prog Biochem Biophys. 2014;41:723–30.Google Scholar
  35. 35.
    Cai B, Wu Z, Liao K, Zhang S. Long noncoding RNA HOTAIR can serve as a common molecular marker for lymph node metastasis: a meta-analysis. Tumour Biol. 2014;35:8445–50.CrossRefPubMedGoogle Scholar
  36. 36.
    Deng K, Guo X, Wang H, Xia J. The lncRNA-MYC regulatory network in cancer. Tumour Biol. 2014;35:9497–503.CrossRefPubMedGoogle Scholar
  37. 37.
    Dong Y, Liang G, Yuan B, Yang C, Gao R, et al. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 2015;36:1477–86.CrossRefPubMedGoogle Scholar
  38. 38.
    Gan L, Xu M, Zhang Y, Zhang X, Guo W. Focusing on long noncoding RNA dysregulation in gastric cancer. Tumour Biol. 2015;36:129–41.CrossRefPubMedGoogle Scholar
  39. 39.
    Gao Y, Chen G, Zeng Y, Zeng J, Lin M, et al. Invasion and metastasis-related long noncoding RNA expression profiles in hepatocellular carcinoma. Tumour Biol. 2015;Google Scholar
  40. 40.
    Guo X, Xia J, Deng K. Long non-coding RNAs: emerging players in gastric cancer. Tumour Biol. 2014;35:10591–600.CrossRefPubMedGoogle Scholar
  41. 41.
    Hajjari M, Khoshnevisan A, Shin YK. Molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer. Tumour Biol. 2014;35:10645–63.CrossRefPubMedGoogle Scholar
  42. 42.
    Slack FJ, Weidhaas JB. MicroRNA in cancer prognosis. N Engl J Med. 2008;359:2720–2.CrossRefPubMedGoogle Scholar
  43. 43.
    Zeng Z, Fan S, Zhang X, Li S, Zhou M, et al. Epstein–Barr virus-encoded small RNA 1 (EBER-1) could predict 3 good prognosis in nasopharyngeal carcinoma. Clin Transl Oncol. 2015;Google Scholar
  44. 44.
    Zeng Z, Bo H, Gong Z, Lian Y, Li X, et al. AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis. Tumour Biol. 2015;Google Scholar
  45. 45.
    Wei F, Li XY, Li XL, Zhang WL, Liao QJ, et al. The effect and mechanism of PLUNC protein family against inflammation and carcinogenesis of nasopharyngeal carcinoma. Prog Biochem Biophys. 2014;41:24–31.Google Scholar
  46. 46.
    Li Y, Lu H. Noncoding RNAs: “our turn” to join the p53 network. J Mol Cell Biol. 2014;6:179–80.CrossRefPubMedGoogle Scholar
  47. 47.
    Gordon MW, Yan F, Zhong X, Mazumder PB, Xu-Monette ZY, et al. Regulation of p53-targeting microRNAs by polycyclic aromatic hydrocarbons: Implications in the etiology of multiple myeloma. Molecular carcinogenesis. 2014;Google Scholar
  48. 48.
    Kumar M, Lu Z, Takwi AA, Chen W, Callander NS, et al. Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene. 2011;30:843–53.CrossRefPubMedGoogle Scholar
  49. 49.
    Ma X, Choudhury SN, Hua X, Dai Z, Li Y. Interaction of the oncogenic miR-21 microRNA and the p53 tumor suppressor pathway. Carcinogenesis. 2013;34:1216–23.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Takwi A, Li Y. The p53 pathway encounters the microRNA world. Current genomics. 2009;10:194–7.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27:4373–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Deng Q, Becker L, Ma X, Zhong X, Young K, et al. The dichotomy of p53 regulation by noncoding RNAs. J Mol Cell Biol. 2014;6:198–205.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Luo Z, Zhang L, Li Z, Li X, Li G, et al. An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma. BMC Med Genomics. 2012;5:3.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Sengupta S, den Boon JA, Chen IH, Newton MA, Dahl DB, et al. Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma. Cancer Res. 2006;66:7999–8006.CrossRefPubMedGoogle Scholar
  55. 55.
    Yang QQ, Deng YF. Genome-wide analysis of long non-coding RNA in primary nasopharyngeal carcinoma by microarray. Histopathology. 2015;66:1022–30.CrossRefPubMedGoogle Scholar
  56. 56.
    Zeng Z, Huang H, Huang L, Sun M, Yan Q, et al. Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas. Sci China Life Sci. 2014;57:315–26.CrossRefPubMedGoogle Scholar
  57. 57.
    Soares MR, Huber J, Rios AF, Ramos ES. Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma. Growth Horm IGF Res. 2010;20:295–7.CrossRefPubMedGoogle Scholar
  58. 58.
    Huang HB, Liang F, Xiong W, Li XL, Zeng ZY, et al. Bioinformatics accelerates drug repositioning. Prog Biochem Biophys. 2012;39:35–44.CrossRefGoogle Scholar
  59. 59.
    Liu N, Chen NY, Cui RX, Li WF, Li Y, et al. Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012;13:633–41.CrossRefPubMedGoogle Scholar
  60. 60.
    Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, et al. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A. 2008;105:5874–8.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Chen HC, Chen GH, Chen YH, Liao WL, Liu CY, et al. MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer. 2009;100:1002–11.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Li T, Chen JX, Fu XP, Yang S, Zhang Z, et al. MicroRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep. 2011;25:1353–63.PubMedGoogle Scholar
  63. 63.
    Lin J, Huo R, Xiao L, Zhu X, Xie J, et al. A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014;66:49–59.CrossRefPubMedGoogle Scholar
  64. 64.
    Subramanian M, Francis P, Bilke S, Li XL, Hara T, et al. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis. Oncogene. 2015;34:1094–104.CrossRefPubMedGoogle Scholar
  65. 65.
    Pan JJ, Zhang SW, Chen CB, Xiao SW, Sun Y, et al. Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27:799–804.CrossRefGoogle Scholar
  66. 66.
    Song SJ, Pandolfi PP. MiR-22 in tumorigenesis. Cell Cycle. 2014;13:11–2.CrossRefPubMedGoogle Scholar
  67. 67.
    Liu XF, Xia YF, Li MZ, Wang HM, He YX, et al. The effect of p21 antisense oligodeoxynucleotides on the radiosensitivity of nasopharyngeal carcinoma cells with normal p53 function. Cell Biol Int. 2006;30:283–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Nagai MA, Butugan O, Logullo A, Brentani MM. Expression of growth factors, proto-oncogenes, and p53 in nasopharyngeal angiofibromas. Laryngoscope. 1996;106:190–5.CrossRefPubMedGoogle Scholar
  69. 69.
    Poon RY. DNA damage checkpoints in nasopharyngeal carcinoma. Oral Oncol. 2014;50:339–44.CrossRefPubMedGoogle Scholar
  70. 70.
    Xie C, Yuan J, Li H, Li M, Zhao G, et al. NONCODEv4: exploring the world of long non-coding RNA genes. Nucleic Acids Res. 2014;42:D98–103.CrossRefPubMedGoogle Scholar
  71. 71.
    Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142:409–19.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43:621–9.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Liu C, Chen Z, Fang J, Xu A, Zhang W, et al. H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation. Tumour Biol. 2015;Google Scholar
  74. 74.
    Ma C, Nong K, Zhu H, Wang W, Huang X, et al. H19 promotes pancreatic cancer metastasis by derepressing let-7’s suppression on its target HMGA2-mediated EMT. Tumour Biol. 2014;35:9163–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Liu Q, Huang J, Zhou N, Zhang Z, Zhang A, et al. LncRNA loc285194 is a p53-regulated tumor suppressor. Nucleic Acids Res. 2013;41:4976–87.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell. 2011;146:353–8.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Ergun S, Oztuzcu S. Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumour Biol. 2015;36:3129–36.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhaojian Gong
    • 1
    • 2
  • Qian Yang
    • 2
    • 3
    • 4
  • Zhaoyang Zeng
    • 1
    • 2
    • 3
  • Wenling Zhang
    • 2
  • Xiayu Li
    • 3
  • Xuyu Zu
    • 5
  • Hao Deng
    • 3
  • Pan Chen
    • 1
  • Qianjin Liao
    • 1
  • Bo Xiang
    • 1
    • 2
    • 3
  • Ming Zhou
    • 1
    • 2
    • 3
  • Xiaoling Li
    • 1
    • 2
    • 3
  • Yong Li
    • 2
    • 6
  • Wei Xiong
    • 1
    • 2
    • 3
  • Guiyuan Li
    • 1
    • 2
    • 3
  1. 1.Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina
  2. 2.Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research InstituteCentral South UniversityChangshaChina
  3. 3.Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.School of Nursing, Hunan Polytechnic of Environment and BiologyHengyangChina
  5. 5.Clinical Research Institution, the First Affiliated HospitalUniversity of South ChinaHengyangChina
  6. 6.Department of Cancer Biology, Lerner Research Institute, Cleveland ClinicClevelandUSA

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