DOI QR코드

DOI QR Code

Involvement of EBV-encoded BART-miRNAs and Dysregulated Cellular miRNAs in Nasopharyngeal Carcinoma Genesis

  • Xie, Yuan-Jie (Cancer Research Institute, University of South China) ;
  • Long, Zhi-Feng (Micromorphology Laboratory Center, University of South China) ;
  • He, Xiu-Sheng (Cancer Research Institute, University of South China)
  • Published : 2013.10.30

Abstract

The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.

Keywords

EBV-encoded BART-miRNAs;carcinogenesis;miRNAs;nasopharyngeal carcinoma

References

  1. Akao Y, Nakagawa Y, Naoe T (2006). let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull, 29, 903-6. https://doi.org/10.1248/bpb.29.903
  2. Alajez NM, Lenarduzzi M, Ito E, et al (2011). MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer Res, 71, 2381-91. https://doi.org/10.1158/0008-5472.CAN-10-2754
  3. Cameron JE, Yin Q, Fewell C, et al (2008). Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 82, 1946-58. https://doi.org/10.1128/JVI.02136-07
  4. Alajez NM, Shi W, Hui AB, et al (2010). Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98. Cell Death Dis, 1, e85. https://doi.org/10.1038/cddis.2010.64
  5. Barth S, Meister G, Grasser FA (2011). EBV-encoded miRNAs. Biochim Biophys Acta, 1809, 631-40. https://doi.org/10.1016/j.bbagrm.2011.05.010
  6. Cai X, Schafer A, Lu S, et al (2006). Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog, 2, e23. https://doi.org/10.1371/journal.ppat.0020023
  7. Cao JY, Mansouri S, Frappier L (2012). Changes in the nasopharyngeal carcinoma nuclear proteome induced by the EBNA1 protein of Epstein-Barr virus reveal potential roles for EBNA1 in metastasis and oxidative stress responses. J Virol, 86, 382-94. https://doi.org/10.1128/JVI.05648-11
  8. Cao SM, Simons MJ, Qian CN (2011). The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer, 30, 114-9. https://doi.org/10.5732/cjc.010.10377
  9. Chan JY, Gao W, Ho WK, Wei WI, Wong TS (2012). Overexpression of Epstein-Barr virus-encoded microRNA-BART7 in undifferentiated nasopharyngeal carcinoma. Anticancer Res, 32, 3201-10.
  10. Chen HC, Chen GH, Chen YH, et al (2009). MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer, 100, 1002-11. https://doi.org/10.1038/sj.bjc.6604948
  11. Chen L, Tang Y, Wang J, Yan Z, Xu R (2013). miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4. Biochem Biophys Res Commun, 435, 745-50. https://doi.org/10.1016/j.bbrc.2013.05.056
  12. Cosmopoulos K, Pegtel M, Hawkins J, et al (2009). Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal carcinoma. J Virol, 83, 2357-67. https://doi.org/10.1128/JVI.02104-08
  13. Chen SJ, Chen GH, Chen YH, et al (2010). Characterization of Epstein-Barr virus miRNAome in nasopharyngeal carcinoma by deep sequencing. PLoS One, 5, doi:pii: e12745. 10.1371/journal.pone.0012745. https://doi.org/10.1371/journal.pone.0012745
  14. Cho WC (2007). Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer, 6, doi:10.1186/1476-4598-6-1 https://doi.org/10.1186/1476-4598-6-1
  15. Choy EY, Siu KL, Kok KH, et al (2008). An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J Exp Med, 205, 2551-60. https://doi.org/10.1084/jem.20072581
  16. Dawson CW, Port RJ, Young LS (2012). The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol, 22, 144-53. https://doi.org/10.1016/j.semcancer.2012.01.004
  17. Deng M, Tang H, Zhou Y, et al (2011). miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma. J Cell Sci, 124, 2997-3005. https://doi.org/10.1242/jcs.085050
  18. Deng M, Ye Q, Qin Z, et al (2013). miR-214 promotes tumorigenesis by targeting lactotransferrin in nasopharyngeal carcinoma. Tumour Biol, 34, 1793-800. https://doi.org/10.1007/s13277-013-0718-y
  19. Dolken L, Malterer G, Erhard F, et al (2010). Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay. Cell Host Microbe, 7, 324-34. https://doi.org/10.1016/j.chom.2010.03.008
  20. Du ZM, Hu LF, Wang HY, et al (2011). Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS One, 6, e19137. https://doi.org/10.1371/journal.pone.0019137
  21. Guo X, Liao Q, Chen P, et al (2012). The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma. J Cancer Res Clin Oncol, 138, 49-56. https://doi.org/10.1007/s00432-011-1058-1
  22. Edwards RH, Marquitz AR, Raab-Traub N (2008). Epstein-Barr virus BART microRNAs are produced from a large intron prior to splicing. J Virol, 82, 9094-106. https://doi.org/10.1128/JVI.00785-08
  23. Farazi TA, Hoell JI, Morozov P, Tuschl T (2013). MicroRNAs in human cancer. Adv Exp Med Biol, 774, 1-20. https://doi.org/10.1007/978-94-007-5590-1_1
  24. Garzon R, Marcucci G, Croce CM (2010). Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov, 9, 775-89. https://doi.org/10.1038/nrd3179
  25. He ML, Luo MX, Lin MC, Kung HF (2012). MicroRNAs: potential diagnostic markers and therapeutic targets for EBV-associated nasopharyngeal carcinoma. Biochim Biophys Acta, 1825, 1-10.
  26. Hennessey PT, Sanford T, Choudhary A, et al (2012). Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One, 7, e32307. https://doi.org/10.1371/journal.pone.0032307
  27. Hui AB, Bruce JP, Alajez NM, et al (2011). Significance of dysregulated metadherin and microRNA-375 in head and neck cancer. Clin Cancer Res, 17, 7539-50. https://doi.org/10.1158/1078-0432.CCR-11-2102
  28. Jr Meckes DG, Shair KH, Marquitz AR, et al (2010). Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci U S A, 107, 20370-5. https://doi.org/10.1073/pnas.1014194107
  29. Kim DN, Chae HS, Oh ST, et al (2007). Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. J Virol, 81, 1033-6. https://doi.org/10.1128/JVI.02271-06
  30. Kim DN, Lee SK (2012). Biogenesis of Epstein-Barr virus microRNAs. Mol Cell Biochem, 365, 203-10. https://doi.org/10.1007/s11010-012-1261-7
  31. Kok KH, Lei T, Jin DY (2010). Identification and validation of the cellular targets of virus-encoded microRNAs. Methods Mol Biol, 667, 319-26. https://doi.org/10.1007/978-1-60761-811-9_21
  32. Li T, Chen JX, Fu XP, et al (2011). microRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep, 25, 1353-63.
  33. Li G, Liu Y, Su Z, et al (2013). MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B. Eur J Cancer, doi: 10.1016/j.ejca.2013.03.001. https://doi.org/10.1016/j.ejca.2013.03.001
  34. Li G, Wu Z, Peng Y, Liu X, et al (2010). MicroRNA-10b induced by Epstein-Barr virus-encoded latent membrane protein-1 promotes the metastasis of human nasopharyngeal carcinoma cells. Cancer Lett, 299, 29-36. https://doi.org/10.1016/j.canlet.2010.07.021
  35. Li JX, Lu TX, Huang Y, Han F (2012). Clinical characteristics of recurrent nasopharyngeal carcinoma in high-incidence area. Sci World J, doi: 10.1100/2012/719754 https://doi.org/10.1100/2012/719754
  36. LIANG BJ, LI XP, LU J, et al (2012). [Effects of enhancer of zeste homolog (EZH2) downregulation on the proliferation and invasion of nasopharyngeal carcinoma cell and the possible mechanisms]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 47, 298-304.
  37. Liu N, Chen NY, Cui RX, et al (2012). Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol, 13, 633-41. https://doi.org/10.1016/S1470-2045(12)70102-X
  38. Liu X, Lv XB, Wang XP, et al (2012). MiR-138 suppressed nasopharyngeal carcinoma growth and tumorigenesis by targeting the CCND1 oncogene. Cell Cycle, 11, 2495-506. https://doi.org/10.4161/cc.20898
  39. Lo AK, Dawson CW, Jin DY, Lo KW (2012). The pathological roles of BART miRNAs in nasopharyngeal carcinoma. J Pathol, 227, 392-403. https://doi.org/10.1002/path.4025
  40. Lo AK, To KF, Lo KW, et al (2007). Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A, 104,16164-9. https://doi.org/10.1073/pnas.0702896104
  41. Luo Z, Zhang L, Li Z, et al (2012). An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma. BMC Med Genomics, doi: 10.1186/1755-8794-5-3. https://doi.org/10.1186/1755-8794-5-3
  42. Lu J, He ML, Wang L, et al (2011). MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res, 71, 225-33. https://doi.org/10.1158/0008-5472.CAN-10-1850
  43. Lung RW, Wang X, Tong JH, et al (2012). A single nucleotide polymorphism in microRNA-146a is associated with the risk for nasopharyngeal carcinoma. Mol Carcinog, doi:10.1002/mc.21937. https://doi.org/10.1002/mc.21937
  44. Luo Z, Dai Y, Zhang L, et al (2013). miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma. Carcinogenesis, 34, 415-25. https://doi.org/10.1093/carcin/bgs329
  45. Marquitz AR, Mathur A, Nam CS, Raab-Traub N (2011). The Epstein-Barr Virus BART microRNAs target the proapoptotic protein Bim. Virology, 412, 392-400. https://doi.org/10.1016/j.virol.2011.01.028
  46. Marquitz AR, Raab-Traub N (2012). The role of miRNAs and EBV BARTs in NPC. Semin Cancer Biol, 22,166-72. https://doi.org/10.1016/j.semcancer.2011.12.001
  47. Mei J, Bachoo R, Zhang CL (2011). MicroRNA-146a inhibits glioma development by targeting Notch1. Mol Cell Biol, 31,3584-92. https://doi.org/10.1128/MCB.05821-11
  48. Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009). Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe, 5, 376-85. https://doi.org/10.1016/j.chom.2009.03.003
  49. Ng WT, Lee MC, Hung WM, et al (2011). Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys, 79, 420-8. https://doi.org/10.1016/j.ijrobp.2009.11.024
  50. Pan J, Hu H, Zhou Z, et al (2010). Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep, 24, 105-12.
  51. Oh SY, Ju Y, Park H (2009). A highly effective and long-lasting inhibition of miRNAs with PNA-based antisense oligonucleotides. Mol Cells, 28,341-5. https://doi.org/10.1007/s10059-009-0134-8
  52. Ohshima K, Inoue K, Fujiwara A, et al (2010). Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One, 5, e13247. https://doi.org/10.1371/journal.pone.0013247
  53. Paik JH, Jang JY, Jeon YK, et al (2011). MicroRNA-146a downregulates NFkappaB activity via targeting TRAF6 and functions as a tumor suppressor having strong prognostic implications in NK/T cell lymphoma. Clin Cancer Res, 17, 4761-71. https://doi.org/10.1158/1078-0432.CCR-11-0494
  54. Polesel J, Serraino D, Negri E, et al (2013). Consumption of fruit, vegetables, and other food groups and the risk of nasopharyngeal carcinoma. Cancer Causes Control, 24, 1157-65. https://doi.org/10.1007/s10552-013-0195-z
  55. Qu C, Liang Z, Huang J, et al (2012). MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN. Cell Cycle, 11, 785-96. https://doi.org/10.4161/cc.11.4.19228
  56. Qu H, Xu W, Huang Y, Yang S (2011). Circulating miRNAs: promising biomarkers of human cancer. Asian Pac J Cancer Prev, 12, 1117-25.
  57. Sengupta S, den Boon JA, Chen IH, et al (2008). MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A, 105, 5874-8. https://doi.org/10.1073/pnas.0801130105
  58. Shair KH, Schnegg CI, Raab-Traub N (2008). EBV latent membrane protein 1 effects on plakoglobin, cell growth, and migration. Cancer Res, 68, 6997-7005. https://doi.org/10.1158/0008-5472.CAN-08-1178
  59. Wijnhoven BP, Hussey DJ, Watson DI, et al (2010). MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma. Br J Surg, 97, 853-61. https://doi.org/10.1002/bjs.7000
  60. Twu CW, Wang WY, Liang WM, et al (2007). Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys, 67, 130-7. https://doi.org/10.1016/j.ijrobp.2006.07.012
  61. Wang W, Le W, Cho DY, Hwang PH, Upadhyay D (2011). Novel effects of statins in enhancing efficacy of chemotherapy in vitro in nasopharyngeal carcinoma. Int Forum Allergy Rhinol, 1, 284-9. https://doi.org/10.1002/alr.20039
  62. Webb N, Connolly G, Tellam J, Yap AS, Khanna R (2008). Epstein-Barr virus associated modulation of Wnt pathway is not dependent on latent membrane protein-1. PLoS One, 3, e3254. https://doi.org/10.1371/journal.pone.0003254
  63. Wong AM, Kong KL, Tsang JW, Kwong DL, Guan XY (2012). Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs. Cancer, 118, 698-710. https://doi.org/10.1002/cncr.26309
  64. Wong TS, Man OY, Tsang CM, et al (2011). MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression. J Cancer Res Clin Oncol, 137, 415-22. https://doi.org/10.1007/s00432-010-0898-4
  65. Wu CD, Kuo YS, Wu HC, Lin CT (2011). MicroRNA-1 induces apoptosis by targeting prothymosin alpha in nasopharyngeal carcinoma cells. J Biomed Sci, doi: 10.1186/1423-0127-18-80. https://doi.org/10.1186/1423-0127-18-80
  66. Wu H, Mo YY (2009). Targeting miR-205 in breast cancer. Expert Opin Ther Targets, 13, 1439-48. https://doi.org/10.1517/14728220903338777
  67. Xia H, Cheung WK, Sze J, et al (2010). miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and beta-catenin signaling. J Biol Chem, 285, 36995-7004. https://doi.org/10.1074/jbc.M110.133744
  68. Yi C, Wang Q, Wang L, et al (2012). MiR-663, a microRNA targeting p21 (WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma. Oncogene, 31, 4421-33. https://doi.org/10.1038/onc.2011.629
  69. Xia H, Ng SS, Jiang S, et al (2010). miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion. Biochem Biophys Res Commun, 391, 535-41. https://doi.org/10.1016/j.bbrc.2009.11.093
  70. Xia XM, Jin WY, Shi RZ, Zhang YF, Chen J (2010). Clinical significance and the correlation of expression between Let-7 and K-ras in non-small cell lung cancer. Oncol Lett, 1, 1045-1047.
  71. Xu X, Yang H, Huo X (2004). [Expression and significance of PTEN in nasopharyngeal carcinoma]. Lin Chuang Er Bi Yan Hou Ke Za Zhi, 18, 658-9.
  72. Yoshizaki T, Ito M, Murono S, et al (2012). Current understanding and management of nasopharyngeal carcinoma. Auris Nasus Larynx, 39, 137-44. https://doi.org/10.1016/j.anl.2011.02.012
  73. You S, Zhang F, Meng F, et al (2011). EBV-encoded LMP1 increases nuclear beta-catenin accumulation and its transcriptional activity in nasopharyngeal carcinoma. Tumour Biol, 32, 623-30. https://doi.org/10.1007/s13277-011-0161-x
  74. Yu H, Lu J, Zuo L, et al (2012). Epstein-Barr virus downregulates microRNA 203 through the oncoprotein latent membrane protein 1: a contribution to increased tumor incidence in epithelial cells. J Virol, 86, 3088-99. https://doi.org/10.1128/JVI.05901-11
  75. Yu L, Lu J, Zhang B, et al (2013). miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2. Oncol Lett, 5, 1223-8.
  76. Yu X, Zhen Y, Yang H, et al (2013). Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma. Cell Death Dis, 4, e634. https://doi.org/10.1038/cddis.2013.153
  77. Zhang LY, Ho-Fun LV, Wong AM, et al (2013). MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. Carcinogenesis, 34, 454-63. https://doi.org/10.1093/carcin/bgs346
  78. Zeng X, Xiang J, Wu M, et al (2012). Circulating miR-17, miR-20a, miR-29c, and miR-223 combined as non-invasive biomarkers in nasopharyngeal carcinoma. PLoS One, 7, e46367. https://doi.org/10.1371/journal.pone.0046367
  79. Zhang JX, Qian D, Wang FW, et al (2013). MicroRNA-29c enhances the sensitivities of human nasopharyngeal carcinoma to cisplatin-based chemotherapy and radiotherapy. Cancer Lett, 329, 91-8. https://doi.org/10.1016/j.canlet.2012.10.033
  80. Zhang L, Deng T, Li X, et al (2010). microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network. Carcinogenesis, 31, 559-66. https://doi.org/10.1093/carcin/bgp335
  81. Zhong W, He B, Quan T, et al (2013). [Expression of miR-143 in nasopharyngeal carcinoma cell lines and its effect on cell adhesion ability]. Nan Fang Yi Ke Da Xue Xue Bao, 33, 582-5.
  82. Zhou Y, Zheng J, Deng J, et al (2013). A sequence polymorphism in miRNA-608 predicts recurrence after radiotherapy of nasopharyngeal carcinoma. Cancer Res, 73, 5151-62. https://doi.org/10.1158/0008-5472.CAN-13-0395
  83. Zhu JY, Pfuhl T, Motsch N, et al (2009). Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas. J Virol, 83, 3333-41. https://doi.org/10.1128/JVI.01689-08

Cited by

  1. Glycididazole Sodium Combined with Radiochemotherapy for Locally Advanced Nasopharyngeal Carcinoma vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2641
  2. Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10355
  3. Understanding the interplay between host immunity and Epstein-Barr virus in NPC patients vol.4, pp.3, 2015, https://doi.org/10.1038/emi.2015.20
  4. Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma vol.11, pp.9, 2016, https://doi.org/10.1371/journal.pone.0163609
  5. Downregulation of miR-429 and inhibition of cell migration and invasion in nasopharyngeal carcinoma vol.13, pp.4, 2016, https://doi.org/10.3892/mmr.2016.4940
  6. BART miRNAs vol.26, pp.2, 2017, https://doi.org/10.1097/CEJ.0000000000000221
  7. Dysregulated miR-27a-3p promotes nasopharyngeal carcinoma cell proliferation and migration by targeting Mapk10 vol.37, pp.5, 2017, https://doi.org/10.3892/or.2017.5544