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LincRNA-p21 predicts favorable clinical outcome and impairs tumorigenesis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy

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Abstract

Despite improved survival for the patients with diffuse large B cell lymphoma (DLBCL), the prognosis after relapse is poor. LincRNA-p21 is a long intergenic noncoding RNA, which is located on chromosome 17, approximately 15 kb upstream from the Cdkn1a (p21) gene. However, its clinical importance and biological role in DLBCL prognosis are unknown. In this study, we conducted quantitative reverse-transcription polymerase chain reaction to investigate the lincRNA-p21 expression in DLBCL. We found that lincRNA-p21 levels were markedly decreased in DLBCL tissues compared with normal. Its expression level was significantly correlated with Ann Arbor stages, B symptoms, performance status, IPI score and serum LDH. Moreover, patients with high levels of LincRNA-p21 expression had a favorable overall survival and progression-free survival. Furthermore, ectopic expression of lincRNA-p21 inhibited cell proliferation, arrested cycle progression and modulated cyclin D1, CDK4 and p21 expression in DLBCL cell lines. These results demonstrated lincRNA-p21 can be identified as a potential novel prognostic biomarker for prognosis in DLBCL and regulate cell proliferation and cycle in vitro. Our findings highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.

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References

  1. Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013;87(2):146–71.

    Article  PubMed  Google Scholar 

  2. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23(18):4117–26.

    Article  CAS  PubMed  Google Scholar 

  3. Lee HJ, Shin DH, Kim KB, Shin N, Park WY, Lee JH, et al. Polycomb protein EZH2 expression in diffuse large B-cell lymphoma is associated with better prognosis in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leuk Lymphoma. 2014;55(9):2056–63. doi:10.3109/10428194.2013.858816.

    Article  CAS  PubMed  Google Scholar 

  4. Vaidya R, Witzig TE. Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann Oncol. 2014;25(11):2124–33. doi:10.1093/annonc/mdu109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hu Y, Ding N, Jin X, Feng L, Ping L, Song Y, et al. Genetic polymorphisms of STAT3 correlated with prognosis in diffuse large B-cell lymphoma patients treated with rituximab. Cancer Cell Int. 2014;14(1):25.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Taskinen M, Louhimo R, Koivula S, Chen P, Rantanen V, Holte H, et al. Deregulation of COMMD1 is associated with poor prognosis in diffuse large B-cell lymphoma. PLoS One. 2014;9(3):e91031. doi:10.1371/journal.pone.0091031.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11(1):12–23. doi:10.1038/nrclinonc.2013.197.

    Article  CAS  PubMed  Google Scholar 

  8. Koh YW, Park C-S, Yoon DH, Suh C, Huh J. Should the cut-off values of the lymphocyte to monocyte ratio for prediction of prognosis in diffuse large B-cell lymphoma be changed in elderly patients? Eur J Haematol. 2014;93(4):340–8. doi:10.1111/ejh.12354.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Tsai M-C, 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  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tsai M-C, 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 

  12. Feng S, Yao J, Chen Y, Geng P, Zhang H, Ma X, et al. Expression and functional role of reprogramming-related long noncoding RNA (lincRNA-ROR) in glioma. J Mol Neurosci. 2015;. doi:10.1007/s12031-014-0488-z.

    Google Scholar 

  13. Hall JR, Messenger ZJ, Tam HW, Phillips SL, Recio L, Smart RC. Long noncoding RNA lincRNA-p21 is the major mediator of UVB-induced and p53-dependent apoptosis in keratinocytes. Cell Death Dis. 2015;6:e1700. doi:10.1038/cddis.2015.67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19. doi:10.1016/j.cell.2010.06.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yoon JH, Abdelmohsen K, Srikantan S, Yang XL, Martindale JL, De S, et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell. 2012;47(4):648–55. doi:10.1016/j.molcel.2012.06.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang GY, Li ZW, Zhao Q, Zhu YY, Zhao C, Li X, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/beta-catenin signaling pathway. Oncol Rep. 2014;31(4):1839–45. doi:10.3892/or.2014.3047.

    CAS  PubMed  Google Scholar 

  17. Dimitrova N, Zamudio JR, Jong RM, Soukup D, Resnick R, Sarma K, et al. LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint. Mol Cell. 2014;54(5):777–90. doi:10.1016/j.molcel.2014.04.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer. Med Oncol. 2014;31(12):346. doi:10.1007/s12032-014-0346-4.

    Article  PubMed  Google Scholar 

  19. Peng W, Wu G, Fan H, Wu J, Feng J. Long noncoding RNA SPRY4-IT1 predicts poor patient prognosis and promotes tumorigenesis in gastric cancer. Tumour Biol. 2015;. doi:10.1007/s13277-015-3376-4.

    Google Scholar 

  20. Peng W, Zhang J, Liu J. URG11 predicts poor prognosis of pancreatic cancer by enhancing epithelial-mesenchymal transition-driven invasion. Med Oncol. 2014;31(7):64. doi:10.1007/s12032-014-0064-y.

    Article  PubMed  Google Scholar 

  21. Lossos IS. Molecular pathogenesis of diffuse large B-cell lymphoma. J Clin Oncol. 2005;23(26):6351–7. doi:10.1200/jco.2005.05.012.

    Article  CAS  PubMed  Google Scholar 

  22. Martelli M, Ferreri AJM, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013;87(2):146–71. doi:10.1016/j.critrevonc.2012.12.009.

    Article  PubMed  Google Scholar 

  23. Lossos IS, Morgensztern D. Prognostic biomarkers in diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(6):995–1007. doi:10.1200/jco.2005.02.4786.

    Article  CAS  PubMed  Google Scholar 

  24. Peng W, Fan H, Wu G, Wu J, Feng J. Upregulation of long noncoding RNA PEG10 associates with poor prognosis in diffuse large B cell lymphoma with facilitating tumorigenicity. Clin Exp Med. 2015. doi:10.1007/s10238-015-0350-9

    Google Scholar 

  25. Barnes DM. Cyclin D1 in mammary carcinoma. J Pathol. 1997;181(3):267–9. doi:10.1002/(sici)1096-9896(199703)181:3<267:aid-path783>3.0.co;2-x.

    Article  CAS  PubMed  Google Scholar 

  26. Nakamura S, Yatabe Y, Seto M. Cyclin D1 overexpression in malignant lymphomas. Pathol Int. 1997;47(7):421–9. doi:10.1111/j.1440-1827.1997.tb04519.x.

    Article  CAS  PubMed  Google Scholar 

  27. Kitagawa M, Higashi H, Jung HK, SuzukiTakahashi I, Ikeda M, Tamai K, et al. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996;15(24):7060–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Kumar R, Gururaj AE, Barnes CJ. p21-activated kinases in cancer. Nat Rev Cancer. 2006;6(6):459–71. doi:10.1038/nrc1892.

    Article  CAS  PubMed  Google Scholar 

  29. Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 2009;9(6):400–14. doi:10.1038/nrc2657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by grants from Agency of Jiangsu Province Science and Technology (No. 2013035) and Research Office of Jiangsu Cancer Hospital (No. ZK201401).

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Correspondence to Jifeng Feng.

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Peng, W., Wu, J. & Feng, J. LincRNA-p21 predicts favorable clinical outcome and impairs tumorigenesis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy. Clin Exp Med 17, 1–8 (2017). https://doi.org/10.1007/s10238-015-0396-8

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  • DOI: https://doi.org/10.1007/s10238-015-0396-8

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