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01.06.2014 | Original Article

Histone deacetylase inhibitor prevents cell growth in Burkitt’s lymphoma by regulating PI3K/Akt pathways and leads to upregulation of miR-143, miR-145, and miR-101

verfasst von: Ana Carolina dos Santos Ferreira, Marcela Cristina Robaina, Lídia Maria Magalhães de Rezende, Patricia Severino, Claudete Esteves Klumb

Erschienen in: Annals of Hematology | Ausgabe 6/2014

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Abstract

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma more common in children comprising one third of pediatric non-Hodgkin lymphoma cases. The recent discovery in BL pathogenesis highlighted the activation of PI3K pathway in cooperation with Myc in the development of BL. In this study, we demonstrated that PI3K/Akt pathway is a target to histone deacetylase inhibitor (HDACi) in BL cells. The combination of HDACi (sodium butyrate, NaB) and chemotherapy (VP-16) inhibited 51 % of the proliferation and enhanced the blockage of the cell cycle progression at G2/M with a concurrent decrease in the S phase. Microarray profiling showed a synergistic action of NaB/VP-16 combination through the differential regulation of 1,413 genes. Comparing VP-16 treatment with the NaB/VP-16 combination, 318 genes were deregulated: 250 genes were downregulated, and 68 were upregulated when compared with untreated cells. Among these genes, six (CDKN1A, CCND1, FAS, CHEK2, MDM4, and SESN2) belong to the p53-signaling pathway. The activation of this signaling pathway is usually induced by stress signals and ultimately leads to cell cycle arrest. Besides, the inhibition of the cell growth was related to reduced Akt phosphorylation, and decrease of c-Myc protein expression by about 60 % (p ≤ 0.005). Moreover, HDACi enhanced miR-101, miR-143, and miR-145 levels in BL cell line, which were inversely associated with the levels of miR-101, miR-143, and miR-145 found to be extremely downregulated in the sample of BL patients. We highlight the fact that effective combinations of HDACis with other target drugs could improve BL therapy in the future.

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Gross TG, Termuhlen AM (2007) Pediatric non-Hodgkin’s lymphoma. Curr Oncol Rep 9(6):459–465CrossRefPubMed

Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35. doi:10.1016/j.cell.2012.03.003 PubMedCentralCrossRefPubMed

Klapproth K, Wirth T (2010) Advances in the understanding of MYC-induced lymphomagenesis. Br J Haematol 149(4):484–497. doi:10.1111/j.1365-2141.2010.08159.x CrossRefPubMed

Meyer N, Kim SS, Penn LZ (2006) The Oscar-worthy role of Myc in apoptosis. Semin Cancer Biol 16(4):275–287. doi:10.1016/j.semcancer.2006.07.011 CrossRefPubMed

Hecht JL, Aster JC (2000) Molecular biology of Burkitt’s lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 18(21):3707–3721

Klumb CE, Furtado DR, de Resende LM, Carrico MK, Coelho AM, de Meis E, Maia RC, Rumjanek FD (2003) DNA sequence profile of TP53 gene mutations in childhood B-cell non-Hodgkin’s lymphomas: prognostic implications. Eur J Haematol 71(2):81–90CrossRefPubMed

Paschos K, Parker GA, Watanatanasup E, White RE, Allday MJ (2012) BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV. Nucleic Acids Res 40(15):7233–7246. doi:10.1093/nar/gks391 PubMedCentralCrossRefPubMed

Paschos K, Smith P, Anderton E, Middeldorp JM, White RE, Allday MJ (2009) Epstein-Barr virus latency in B cells leads to epigenetic repression and CpG methylation of the tumour suppressor gene Bim. PLoS Pathog 5(6):e1000492. doi:10.1371/journal.ppat.1000492 PubMedCentralCrossRefPubMed

Sander S, Calado DP, Srinivasan L, Kochert K, Zhang B, Rosolowski M, Rodig SJ, Holzmann K, Stilgenbauer S, Siebert R, Bullinger L, Rajewsky K (2012) Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Cancer Cell 22(2):167–179. doi:10.1016/j.ccr.2012.06.012 PubMedCentralCrossRefPubMed

10.

Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, Staudt LM (2012) Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 490(7418):116–120. doi:10.1038/nature11378 PubMedCentralCrossRefPubMed

11.

Carnero A (2010) The PKB/AKT pathway in cancer. Curr Pharm Des 16(1):34–44CrossRefPubMed

12.

Rasul A, Ding C, Li X, Khan M, Yi F, Ali M, Ma T (2012) Dracorhodin perchlorate inhibits PI3K/Akt and NF-kappaB activation, up-regulates the expression of p53, and enhances apoptosis. Apoptosis: Int J Programmed Cell Death 17(10):1104–1119. doi:10.1007/s10495-012-0742-1 CrossRef

13.

Lee KB, Byun HJ, Park SH, Park CY, Lee SH, Rho SB (2012) CYR61 controls p53 and NF-kappaB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. Cancer Lett 315(1):86–95. doi:10.1016/j.canlet.2011.10.016 CrossRefPubMed

14.

Klangby U, Okan I, Magnusson KP, Wendland M, Lind P, Wiman KG (1998) p16/INK4a and p15/INK4b gene methylation and absence of p16/INK4a mRNA and protein expression in Burkitt’s lymphoma. Blood 91(5):1680–1687PubMed

15.

de Yebenes VG, Bartolome-Izquierdo N, Ramiro AR (2013) Regulation of B-cell development and function by microRNAs. Immunol Rev 253(1):25–39. doi:10.1111/imr.12046 PubMedCentralCrossRefPubMed

16.

Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6(6):590–610. doi:10.1016/j.molonc.2012.09.006 CrossRefPubMed

17.

Dos Santos Ferreira AC, Fernandes RA, Kwee JK, Klumb CE (2012) Histone deacetylase inhibitor potentiates chemotherapy-induced apoptosis through Bim upregulation in Burkitt’s lymphoma cells. J Cancer Res Clin Oncol 138(2):317–325. doi:10.1007/s00432-011-1093-y CrossRefPubMed

18.

Vasiljevic N, Wu K, Brentnall AR, Kim DC, Thorat MA, Kudahetti SC, Mao X, Xue L, Yu Y, Shaw GL, Beltran L, Lu YJ, Berney DM, Cuzick J, Lorincz AT (2011) Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing. Dis Markers 30(4):151–161. doi:10.3233/DMA-2011-0790 CrossRefPubMed

19.

Bader AG, Kang S, Zhao L, Vogt PK (2005) Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 5(12):921–929. doi:10.1038/nrc1753 CrossRefPubMed

20.

Ou JN, Torrisani J, Unterberger A, Provencal N, Shikimi K, Karimi M, Ekstrom TJ, Szyf M (2007) Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochem Pharmacol 73(9):1297–1307. doi:10.1016/j.bcp.2006.12.032 CrossRefPubMed

21.

Crump M, Coiffier B, Jacobsen ED, Sun L, Ricker JL, Xie H, Frankel SR, Randolph SS, Cheson BD (2008) Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 19(5):964–969. doi:10.1093/annonc/mdn031 CrossRef

22.

Tan J, Cang S, Ma Y, Petrillo RL, Liu D (2010) Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol 3:5. doi:10.1186/1756-8722-3-5 PubMedCentralCrossRefPubMed

23.

Siegel D, Hussein M, Belani C, Robert F, Galanis E, Richon VM, Garcia-Vargas J, Sanz-Rodriguez C, Rizvi S (2009) Vorinostat in solid and hematologic malignancies. J Hematol Oncol 2:31. doi:10.1186/1756-8722-2-31 PubMedCentralCrossRefPubMed

24.

Atra A, Gerrard M, Hobson R, Imeson JD, Hann IM, Pinkerton CR (2001) Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin’s lymphoma treated with the UKCCSG 9003/9002 protocols. Br J Haematol 112(4):965–968CrossRefPubMed

25.

Cairo MS, Sposto R, Perkins SL, Meadows AT, Hoover-Regan ML, Anderson JR, Siegel SE, Lones MA, Tedeschi-Blok N, Kadin ME, Kjeldsberg CR, Wilson JF, Sanger W, Morris E, Krailo MD, Finlay JL (2003) Burkitt’s and Burkitt-like lymphoma in children and adolescents: a review of the Children’s Cancer Group experience. Br J Haematol 120(4):660–670CrossRefPubMed

26.

Griffin TC, Weitzman S, Weinstein H, Chang M, Cairo M, Hutchison R, Shiramizu B, Wiley J, Woods D, Barnich M, Gross TG (2009) A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Pediatr Blood Cancer 52(2):177–181. doi:10.1002/pbc.21753 PubMedCentralCrossRefPubMed

27.

Lambert MP, Herceg Z (2008) Epigenetics and cancer, 2nd IARC meeting, Lyon, France, 6 and 7 December 2007. Mol Oncol 2(1):33–40. doi:10.1016/j.molonc.2008.03.005 CrossRefPubMed

28.

Shao W, Growney JD, Feng Y, O’Connor G, Pu M, Zhu W, Yao YM, Kwon P, Fawell S, Atadja P (2010) Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: defining molecular mechanisms of resistance. Int J Cancer J Int Du Cancer 127(9):2199–2208. doi:10.1002/ijc.25218 CrossRef

29.

Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O’Brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP (2006) Phase 1/2 study of the combination of 5-aza-2’-deoxycytidine with valproic acid in patients with leukemia. Blood 108(10):3271–3279. doi:10.1182/blood-2006-03-009142 PubMedCentralCrossRefPubMed

30.

Dominguez-Sola D, Dalla-Favera R (2012) Burkitt lymphoma: much more than MYC. Cancer Cell 22(2):141–142. doi:10.1016/j.ccr.2012.07.018 CrossRefPubMed

31.

Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296(5573):1655–1657. doi:10.1126/science.296.5573.1655 CrossRefPubMed

32.

Jasek E, Lis GJ, Jasinska M, Jurkowska H, Litwin JA (2012) Effect of histone deacetylase inhibitors trichostatin A and valproic acid on etoposide-induced apoptosis in leukemia cells. Anticancer Res 32(7):2791–2799PubMed

33.

Guan H, Xie L, Klapproth K, Weitzer CD, Wirth T, Ushmorov A (2013) Decitabine represses translocated MYC oncogene in Burkitt lymphoma. J Pathol 229(5):775–783. doi:10.1002/path.4164 CrossRefPubMed

34.

Milutinovic S, D’Alessio AC, Detich N, Szyf M (2007) Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis 28(3):560–571. doi:10.1093/carcin/bgl167 PubMed

35.

Schwartz B, Avivi-Green C, Polak-Charcon S (1998) Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells. Mol Cell Biochem 188(1–2):21–30CrossRefPubMed

36.

Sanchez-Beato M, Sanchez-Aguilera A, Piris MA (2003) Cell cycle deregulation in B-cell lymphomas. Blood 101(4):1220–1235. doi:10.1182/blood-2002-07-2009 CrossRefPubMed

37.

Iio A, Nakagawa Y, Hirata I, Naoe T, Akao Y (2010) Identification of non-coding RNAs embracing microRNA-143/145 cluster. Mol Cancer 9:136. doi:10.1186/1476-4598-9-136 PubMedCentralCrossRefPubMed

38.

Di Lisio L, Sanchez-Beato M, Gomez-Lopez G, Rodriguez ME, Montes-Moreno S, Mollejo M, Menarguez J, Martinez MA, Alves FJ, Pisano DG, Piris MA, Martinez N (2012) MicroRNA signatures in B-cell lymphomas. Blood Cancer J 2(2):e57. doi:10.1038/bcj.2012.1 PubMedCentralCrossRefPubMed

39.

Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T (2010) Role of anti-oncomirs miR-143 and -145 in human colorectal tumors. Cancer Gene Ther 17(6):398–408. doi:10.1038/cgt.2009.88 CrossRefPubMed

40.

Akao Y, Nakagawa Y, Kitade Y, Kinoshita T, Naoe T (2007) Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci 98(12):1914–1920. doi:10.1111/j.1349-7006.2007.00618.x CrossRefPubMed

41.

Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, Elble R, Watabe K, Mo YY (2009) p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 106(9):3207–3212. doi:10.1073/pnas.0808042106 PubMedCentralCrossRefPubMed

42.

He XP, Shao Y, Li XL, Xu W, Chen GS, Sun HH, Xu HC, Xu X, Tang D, Zheng XF, Xue YP, Huang GC, Sun WH (2012) Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth. FEBS J 279(22):4201–4212. doi:10.1111/febs.12013 CrossRefPubMed

43.

Wang HJ, Ruan HJ, He XJ, Ma YY, Jiang XT, Xia YJ, Ye ZY, Tao HQ (2010) MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer 46(12):2295–2303. doi:10.1016/j.ejca.2010.05.012 CrossRefPubMed

44.

Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Wurdinger T (2010) miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget 1(8):710–720PubMedCentralPubMed

45.

Cho HM, Jeon HS, Lee SY, Jeong KJ, Park SY, Lee HY, Lee JU, Kim JH, Kwon SJ, Choi E, Na MJ, Kang J, Son JW (2011) microRNA-101 inhibits lung cancer invasion through the regulation of enhancer of zeste homolog 2. Exp Ther Med 2(5):963–967. doi:10.3892/etm.2011.284 PubMedCentralPubMed

46.

Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, Dang CV, Thomas-Tikhonenko A, Mendell JT (2008) Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 40(1):43–50. doi:10.1038/ng.2007.30 PubMedCentralCrossRefPubMed

47.

Robertus JL, Kluiver J, Weggemans C, Harms G, Reijmers RM, Swart Y, Kok K, Rosati S, Schuuring E, van Imhoff G, Pals ST, Kluin P, van den Berg A (2010) MiRNA profiling in B non-Hodgkin lymphoma: a MYC-related miRNA profile characterizes Burkitt lymphoma. Br J Haematol 149(6):896–899. doi:10.1111/j.1365-2141.2010.08111.x CrossRefPubMed

48.

Chim CS, Wong KY, Qi Y, Loong F, Lam WL, Wong LG, Jin DY, Costello JF, Liang R (2010) Epigenetic inactivation of the miR-34a in hematological malignancies. Carcinogenesis 31(4):745–750. doi:10.1093/carcin/bgq033 CrossRefPubMed

49.

Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernandez-Piqueras J, Malumbres M (2008) Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 13(6):496–506. doi:10.1016/j.ccr.2008.04.018 CrossRefPubMed

Titel: Histone deacetylase inhibitor prevents cell growth in Burkitt’s lymphoma by regulating PI3K/Akt pathways and leads to upregulation of miR-143, miR-145, and miR-101
verfasst von: Ana Carolina dos Santos Ferreira
Marcela Cristina Robaina
Lídia Maria Magalhães de Rezende
Patricia Severino
Claudete Esteves Klumb
Publikationsdatum: 01.06.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 6/2014
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-014-2021-4

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