Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Research

The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type

Authors: Li Liang, Lin Nong, Shuang Zhang, Jing Zhao, Hongjuan Ti, Ying Dong, Bo Zhang, Ting Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

Login to get access

Abstract

Background

The mechanism for inactivation of positive regulatory domain containing I (PRDM1), a newly identified tumour suppressor gene in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT) has not been well defined. The aim of the present study was to investigate the expression of PRDM1 in EN-NK/T-NT and analyse its downregulation by miRNAs.

Methods

PRDM1 and miRNA expression were evaluated in EN-NK/T-NT samples by immunohistochemical analysis, qRT-PCR, and in situ hybridisation. Luciferase assays were performed to verify the direct binding of miR-223 to the 3′-untranslated region of PRDM1 mRNA. In addition, the effect of miR-223 on PRDM1 expression was assessed in NK/T lymphoma cell lines by transfecting a miR-223 mimic or inhibitor to increase or decrease the effective expression of miR-223. Overall survival and failure-free survival in EN-NK/T-NT patients were analysed using Kaplan-Meier single-factor analysis and the log-rank test.

Results

Investigation of the downregulation of PRDM1 in EN-NK/T-NT cases revealed that PRDM1-positive staining might be a favourable predictor of overall survival and failure-free survival in EN-NK/T-NT patients. However, the negative staining of PRDM1 usually presented transcripts, suggesting a possible post-transcriptional regulation. miR-223 and its putative target gene, PRDM1, exhibited opposite patterns of expression in EN-NK/T-NT tissues and cell lines. Moreover, PRDM1 was identified as a direct target gene of miR-223 by luciferase assays. The ectopic expression of miR-223 led to the downregulation of the PRDM1 protein in the NK/T-cell lymphoma cell line, whereas a decrease in miR-223 restored the level of PRDM1 protein.

Conclusions

Our findings reveal that the downregulation of the tumour suppressor PRDM1 in EN-NK/T-NT samples is mediated by miR-223 and that PRDM1-positive staining might have prognostic value for evaluating the clinical outcome of EN-NK/T-NT patients.
Appendix
Available only for authorised users
Literature
1.
Aozasa K, Takakuwa T, Hongyo T, Yang WI: Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol. 2008, 87: 110-117. 10.1007/s12185-008-0021-7.PubMedCentralCrossRefPubMed
2.
Ren YL, Nong L, Zhang S, Zhao J, Zhang XM, Li T: Analysis of 142 Northern Chinese patients with peripheral T/NK-Cell lymphomas: subtype distribution, clinicopathologic features, and prognosis. Am J Clin Pathol. 2012, 138: 435-447. 10.1309/AJCPWKJ3GPFRT7GA.CrossRefPubMed
3.
Huang Y, de Reynies A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, Bosq J, Briere J, Petit B, Thomas E, et al: Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood. 2010, 115: 1226-1237. 10.1182/blood-2009-05-221275.PubMedCentralCrossRefPubMed
4.
Coppo P, Gouilleux-Gruart V, Huang Y, Bouhlal H, Bouamar H, Bouchet S, Perrot C, Vieillard V, Dartigues P, Gaulard P, et al: STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma. Leukemia. 2009, 23: 1667-1678. 10.1038/leu.2009.91.PubMedCentralCrossRefPubMed
5.
Zhang S, Li T, Zhang B, Nong L, Aozasa K: Transcription factors engaged in development of NK cells are commonly expressed in nasal NK/T-cell lymphomas. Hum Pathol. 2011, 42: 1319-1328. 10.1016/j.humpath.2009.11.022.CrossRefPubMed
6.
Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo YM, Iwamoto K, Yamashita J, Saitoh H, Kameoka Y, Shimizu N, et al: Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood. 2009, 114: 3265-3275. 10.1182/blood-2009-06-222794.CrossRefPubMed
7.
Ng SB, Yan J, Huang G, Selvarajan V, Tay JL, Lin B, Bi C, Tan J, Kwong YL, Shimizu N, et al: Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma. Blood. 2011, 118: 4919-4929. 10.1182/blood-2011-07-364224.CrossRefPubMed
8.
Nakashima Y, Tagawa H, Suzuki R, Karnan S, Karube K, Ohshima K, Muta K, Nawata H, Morishima Y, Nakamura S, Seto M: Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type. Gene Chromosome Canc. 2005, 44: 247-255. 10.1002/gcc.20245.CrossRef
9.
Ko YH, Choi KE, Han JH, Kim JM, Ree HJ: Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma. Cytometry. 2001, 46: 85-91. 10.1002/cyto.1069.CrossRefPubMed
10.
Yoon J, Ko YH: Deletion mapping of the long arm of chromosome 6 in peripheral T and NK cell lymphomas. Leuk Lymphoma. 2003, 44: 2077-2082. 10.1080/1042819031000123410.CrossRefPubMed
11.
Iqbal J, Kucuk C, Deleeuw RJ, Srivastava G, Tam W, Geng H, Klinkebiel D, Christman JK, Patel K, Cao K, et al: Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia. 2009, 23: 1139-1151. 10.1038/leu.2009.3.CrossRefPubMed
12.
Kucuk C, Iqbal J, Hu X, Gaulard P, De Leval L, Srivastava G, Au WY, McKeithan TW, Chan WC: PRDM1 is a tumor suppressor gene in natural killer cell malignancies. Proc Natl Acad Sci U S A. 2011, 108: 20119-20124. 10.1073/pnas.1115128108.PubMedCentralCrossRefPubMed
13.
Karube K, Nakagawa M, Tsuzuki S, Takeuchi I, Honma K, Nakashima Y, Shimizu N, Ko YH, Morishima Y, Ohshima K, et al: Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood. 2011, 118: 3195-3204. 10.1182/blood-2011-04-346890.CrossRefPubMed
14.
Chan JKC, Quintanilla-Martinez L, Ferry JA, Peh SC, et al: Extranodal NK/T-cell lymphoma, nasal type. World Health Organization classification of tumors. WHO classification of tumours of aematopoietic and lymphoid tissues. Edited by: Swerdlow SH. 2008, Lyon, France: IARC Press, 285-288.
15.
Yodoi J, Teshigawara K, Nikaido T, Fukui K, Noma T, Honjo T, Takigawa M, Sasaki M, Minato N, Tsudo M, et al: TCGF (IL 2)-receptor inducing factor(s). I. Regulation of IL 2 receptor on a natural killer-like cell line (YT cells). J Immunol. 1985, 134: 1623-1630.PubMed
16.
Robertson MJ, Cochran KJ, Cameron C, Le JM, Tantravahi R, Ritz J: Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. Exp Hematol. 1996, 24: 406-415.PubMed
17.
Gong JH, Maki G, Klingemann HG: Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994, 8: 652-658.PubMed
18.
Garcia JF, Roncador G, Sanz AI, Maestre L, Lucas E, Montes-Moreno S, Fernandez Victoria R, Martinez-Torrecuadrara JL, Marafioti T, Mason DY, Piris MA: PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma. Haematologica. 2006, 91: 467-474.PubMed
19.
Nie K, Zhang T, Allawi H, Gomez M, Liu Y, Chadburn A, Wang YL, Knowles DM, Tam W: Epigenetic down-regulation of the tumor suppressor gene PRDM1/Blimp-1 in diffuse large B cell lymphomas: a potential role of the microRNA let-7. Am J Pathol. 2010, 177: 1470-1479. 10.2353/ajpath.2010.091291.PubMedCentralCrossRefPubMed
20.
Nie K, Gomez M, Landgraf P, Garcia JF, Liu Y, Tan LH, Chadburn A, Tuschl T, Knowles DM, Tam W: MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas. Am J Pathol. 2008, 173: 242-252. 10.2353/ajpath.2008.080009.PubMedCentralCrossRefPubMed
21.
Ti HJ, Nong L, Wang W, Zhang S, Li T: Expression of microRNA in extranodal NK/T cell lymphoma, nasal type. Zhonghua Bing Li Xue Za Zhi. 2011, 40: 610-615.PubMed
22.
Mandelbaum J, Bhagat G, Tang H, Mo T, Brahmachary M, Shen Q, Chadburn A, Rajewsky K, Tarakhovsky A, Pasqualucci L, Dalla-Favera R: BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. Cancer Cell. 2010, 18: 568-579. 10.1016/j.ccr.2010.10.030.PubMedCentralCrossRefPubMed
23.
Calado DP, Zhang B, Srinivasan L, Sasaki Y, Seagal J, Unitt C, Rodig S, Kutok J, Tarakhovsky A, Schmidt-Supprian M, Rajewsky K: Constitutive canonical NF-kappaB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell. 2010, 18: 580-589. 10.1016/j.ccr.2010.11.024.PubMedCentralCrossRefPubMed
24.
Desai S, Maurin M, Smith MA, Bolick SC, Dessureault S, Tao J, Sotomayor E, Wright KL: PRDM1 is required for mantle cell lymphoma response to bortezomib. Mol Cancer Res. 2010, 8: 907-918. 10.1158/1541-7786.MCR-10-0131.PubMedCentralCrossRefPubMed
25.
Shaffer AL, Yu X, He Y, Boldrick J, Chan EP, Staudt LM: BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity. 2000, 13: 199-212. 10.1016/S1074-7613(00)00020-0.CrossRefPubMed
26.
Vrzalikova K, Vockerodt M, Leonard S, Bell A, Wei W, Schrader A, Wright KL, Kube D, Rowe M, Woodman CB, Murray PG: Down-regulation of BLIMP1alpha by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas. Blood. 2011, 117: 5907-5917. 10.1182/blood-2010-09-307710.PubMedCentralCrossRefPubMed
27.
Kallies A, Carotta S, Huntington ND, Bernard NJ, Tarlinton DM, Smyth MJ, Nutt SL: A role for Blimp1 in the transcriptional network controlling natural killer cell maturation. Blood. 2011, 117: 1869-1879. 10.1182/blood-2010-08-303123.CrossRefPubMed
28.
John SA, Clements JL, Russell LM, Garrett-Sinha LA: Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. J Biol Chem. 2008, 283: 951-962. 10.1074/jbc.M705262200.CrossRefPubMed
29.
Pasqualucci L, Compagno M, Houldsworth J, Monti S, Grunn A, Nandula SV, Aster JC, Murty VV, Shipp MA, Dalla-Favera R: Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med. 2006, 203: 311-317. 10.1084/jem.20052204.PubMedCentralCrossRefPubMed
30.
Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006, 6: 259-269. 10.1038/nrc1840.CrossRefPubMed
31.
Kala R, Peek GW, Hardy TM, Tollefsbol TO: MicroRNAs: an emerging science in cancer epigenetics. J Clin Bioinform. 2013, 3: 6-10.1186/2043-9113-3-6.CrossRef
32.
Ma R, Jiang T, Kang X: Circulating microRNAs in cancer: origin, function and application. J Exp Clin Canc Res. 2012, 31: 38-10.1186/1756-9966-31-38.CrossRef
33.
Gao SM, Xing CY, Chen CQ, Lin SS, Dong PH, Yu FJ: miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level. J Exp Clin Canc Res. 2011, 30: 110-10.1186/1756-9966-30-110.CrossRef
34.
Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, et al: MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci U S A. 2007, 104: 19971-19976. 10.1073/pnas.0709313104.PubMedCentralCrossRefPubMed
35.
Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van Den Neste E, Michaux L, Heimann P, Martiat P, Bron D, Lagneaux L: microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood. 2009, 113: 5237-5245. 10.1182/blood-2008-11-189407.CrossRefPubMed
36.
Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD: Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008, 451: 1125-1129. 10.1038/nature06607.CrossRefPubMed
37.
Pulikkan JA, Dengler V, Peramangalam PS, Peer Zada AA, Muller-Tidow C, Bohlander SK, Tenen DG, Behre G: Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010, 115: 1768-1778. 10.1182/blood-2009-08-240101.PubMedCentralCrossRefPubMed
38.
Liu TY, Chen SU, Kuo SH, Cheng AL, Lin CW: E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response. Mod Pathol. 2010, 23: 1507-1517. 10.1038/modpathol.2010.139.CrossRefPubMed
39.
Chiaretti S, Messina M, Tavolaro S, Zardo G, Elia L, Vitale A, Fatica A, Gorello P, Piciocchi A, Scappucci G, et al: Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia with myeloid-like gene features and over-expression of miR-223. Haematologica. 2010, 95: 1114-1121. 10.3324/haematol.2009.015099.PubMedCentralCrossRefPubMed
40.
Inomata M, Tagawa H, Guo YM, Kameoka Y, Takahashi N, Sawada K: MicroRNA-17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. Blood. 2009, 113: 396-402.CrossRefPubMed
41.
Lee JE, Hong EJ, Nam HY, Kim JW, Han BG, Jeon JP: MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits. Cell Prolif. 2011, 44: 59-66. 10.1111/j.1365-2184.2010.00717.x.CrossRefPubMed
42.
Motsch N, Alles J, Imig J, Zhu J, Barth S, Reineke T, Tinguely M, Cogliatti S, Dueck A, Meister G, et al: MicroRNA profiling of Epstein-Barr virus-associated NK/T-cell lymphomas by deep sequencing. PLoS One. 2012, 7: e42193-10.1371/journal.pone.0042193.PubMedCentralCrossRefPubMed
43.
Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I: A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005, 123: 819-831. 10.1016/j.cell.2005.09.023.CrossRefPubMed
Metadata
Title
The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type
Authors
Li Liang
Lin Nong
Shuang Zhang
Jing Zhao
Hongjuan Ti
Ying Dong
Bo Zhang
Ting Li
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-33-7

Other articles of this Issue 1/2014

Journal of Experimental & Clinical Cancer Research 1/2014 Go to the issue

Research

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

Research

Decreased expression of prenyl diphosphate synthase subunit 2 correlates with reduced survival of patients with gastric cancer

Research

Expression of RABEX-5 and its clinical significance in prostate cancer

Review

Progress in oncolytic virotherapy for the treatment of thyroid malignant neoplasm

Research

MicroRNA-320c inhibits tumorous behaviors of bladder cancer by targeting Cyclin-dependent kinase 6

Review

Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits