Skip to main content
Erschienen in: International Journal of Hematology 6/2017

21.02.2017 | Original Article

Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome

verfasst von: Jing Wen, Ying Huang, Hongying Li, Xupai Zhang, Peng Cheng, Donghong Deng, Zhigang Peng, Jun Luo, Weihua Zhao, Yongrong Lai, Zhenfang Liu

Erschienen in: International Journal of Hematology | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

Abstract

Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis with a high risk of transformation to acute myeloid leukemia (AML). miRNAs function as tumor suppressors and oncogenes in various cancers and regulate the differentiation potential of hematopoietic stem and progenitor cells (HSPCs). It has been suggested that miRNAs may play an important role in progression of MDS. We analyzed bone marrow samples collected from MDS patients according to different risk stratification indicated by the International Prognostic Scoring System (IPSS). We demonstrated that miR-196b-5p was up-regulated in intermediate II and higher groups, and in secondary AML (s-AML) patients in particular (P < 0.01) compared with healthy controls, suggesting that the higher expression levels are associated with increased risk of the development of MDS. We observed changes in proliferation and apoptosis in MDS-L cells following transfection with miR-196-5p mimics or inhibitors. After up-regulating the expression of miR-196b-5p, proliferation of MDS-L cells was up-regulated, whereas apoptosis was down-regulated (P < 0.05). In contrast, down-regulation of miR-196b-5p expression decreased cell proliferation and increased apoptosis (P < 0.05). We concluded that over-expression of miR-196b-5p may be closely associated with the risk of transformation to leukemia in MDS patients.
Literatur
1.
Zurück zum Zitat Visconte V, Tiu RV, Rogers HJ. Pathogenesis of myelodysplastic syndromes: an overview of molecular and non-molecular aspects of the disease. Blood Res. 2014;49(4):216–27.CrossRefPubMedPubMedCentral Visconte V, Tiu RV, Rogers HJ. Pathogenesis of myelodysplastic syndromes: an overview of molecular and non-molecular aspects of the disease. Blood Res. 2014;49(4):216–27.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Issa JP. Epigenetic changes in the myelodysplastic syndromes. Hematol Oncol Clin N Am. 2010;24(2):317–30.CrossRef Issa JP. Epigenetic changes in the myelodysplastic syndromes. Hematol Oncol Clin N Am. 2010;24(2):317–30.CrossRef
3.
Zurück zum Zitat Schemenau J, Balsus S, Anlauf M, Reinecke P, Braunstein S, Blum S, et al. Cellularity, characteristics of hematopoietic parameters and prognosis in myelodysplastic syndromes. Eur J Haematol. 2015;95(3):181–9.CrossRefPubMed Schemenau J, Balsus S, Anlauf M, Reinecke P, Braunstein S, Blum S, et al. Cellularity, characteristics of hematopoietic parameters and prognosis in myelodysplastic syndromes. Eur J Haematol. 2015;95(3):181–9.CrossRefPubMed
4.
Zurück zum Zitat Parker JE, Mufti GJ. The role of apoptosis in the pathogenesis of the myelodysplastic syndromes. Int J Hematol. 2001;73(4):416–28.CrossRefPubMed Parker JE, Mufti GJ. The role of apoptosis in the pathogenesis of the myelodysplastic syndromes. Int J Hematol. 2001;73(4):416–28.CrossRefPubMed
5.
Zurück zum Zitat Shen L, Kantarjian H, Guo Y, Lin E, Shan J, Huang X, et al. DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. J Clin Oncol. 2010;28(4):605–13.CrossRefPubMed Shen L, Kantarjian H, Guo Y, Lin E, Shan J, Huang X, et al. DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. J Clin Oncol. 2010;28(4):605–13.CrossRefPubMed
6.
Zurück zum Zitat Will B, Zhou L, Vogler TO, Ben-Neriah S, Schinke C, Tamari R, et al. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations. Blood. 2012;120(10):2076–86.CrossRefPubMedPubMedCentral Will B, Zhou L, Vogler TO, Ben-Neriah S, Schinke C, Tamari R, et al. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations. Blood. 2012;120(10):2076–86.CrossRefPubMedPubMedCentral
7.
8.
Zurück zum Zitat Nolte F, Hofmann WK. Myelodysplastic syndromes: molecular pathogenesis and genomic changes. Ann Hematol. 2008;87(10):777–95.CrossRefPubMed Nolte F, Hofmann WK. Myelodysplastic syndromes: molecular pathogenesis and genomic changes. Ann Hematol. 2008;87(10):777–95.CrossRefPubMed
9.
Zurück zum Zitat Bally C, Thepot S, Quesnel B, Quesnel B, Vey N, Deryfus F, et al. Azacitidine in the treatment of therapy related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML): a report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM). Leukemia Res. 2013;37(6):637–40.CrossRef Bally C, Thepot S, Quesnel B, Quesnel B, Vey N, Deryfus F, et al. Azacitidine in the treatment of therapy related myelodysplastic syndromes and acute myeloid leukemia (t-MDS/AML): a report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM). Leukemia Res. 2013;37(6):637–40.CrossRef
10.
Zurück zum Zitat Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMed Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMed
11.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed
12.
Zurück zum Zitat Hatfield S, Ruohola-Baker H. MicroRNA and stem cell function. Cell Tissue Res. 2008;331(1):57–66.CrossRefPubMed Hatfield S, Ruohola-Baker H. MicroRNA and stem cell function. Cell Tissue Res. 2008;331(1):57–66.CrossRefPubMed
13.
Zurück zum Zitat Castoldi M, Schmidt S, Benes V, Noerholm M, Kulozik AE, Hentze MW, et al. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA. 2006;12(5):913–20.CrossRefPubMedPubMedCentral Castoldi M, Schmidt S, Benes V, Noerholm M, Kulozik AE, Hentze MW, et al. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA. 2006;12(5):913–20.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
15.
Zurück zum Zitat Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 2011; 17(9):3029–38. Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 2011; 17(9):3029–38.
16.
Zurück zum Zitat Buttke TM, McCubrey JA, Owen TC. Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines. J Immunol Methods. 1993;157(1–2):223–40. Buttke TM, McCubrey JA, Owen TC. Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines. J Immunol Methods. 1993;157(1–2):223–40.
17.
Zurück zum Zitat Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, et al. MicroRNA miR-125a controls hematopoietic stem cell number. Proc Natl Acad Sci USA. 2010;107(32):14229–34.CrossRefPubMedPubMedCentral Guo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, et al. MicroRNA miR-125a controls hematopoietic stem cell number. Proc Natl Acad Sci USA. 2010;107(32):14229–34.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Iwasaki H, Akashi K. Hematopoietic development pathways: on cellular basis. Oncogene. 2007;26(47):6687–96.CrossRefPubMed Iwasaki H, Akashi K. Hematopoietic development pathways: on cellular basis. Oncogene. 2007;26(47):6687–96.CrossRefPubMed
20.
Zurück zum Zitat Doulatov S, Notta F, Laurenti E, Dick JE. Hematopoiesis: a human perspective. Cell Stem Cell. 2012;10(2):120–36.CrossRefPubMed Doulatov S, Notta F, Laurenti E, Dick JE. Hematopoiesis: a human perspective. Cell Stem Cell. 2012;10(2):120–36.CrossRefPubMed
21.
Zurück zum Zitat O’Connell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore D. MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proc Natl Acad Sci USA. 2010;107(32):14235–40.CrossRefPubMedPubMedCentral O’Connell RM, Chaudhuri AA, Rao DS, Gibson WS, Balazs AB, Baltimore D. MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output. Proc Natl Acad Sci USA. 2010;107(32):14235–40.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Sokol L, Caceres G, Volinia S, Alder H, Nuovo GJ, Liu CG, et al. Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes. Br J Haematol. 2011;153(1):24–32.CrossRefPubMedPubMedCentral Sokol L, Caceres G, Volinia S, Alder H, Nuovo GJ, Liu CG, et al. Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes. Br J Haematol. 2011;153(1):24–32.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Bousquet M, Quelen C, Rosati R, Mansat-De Mas V, La Starza R, Bastard C, et al. Myeloid cell differentiation arrest by miR -125b-1 in myelodysplastic syndromes and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. J Exp Med. 2008;205(11):2499–506.CrossRefPubMedPubMedCentral Bousquet M, Quelen C, Rosati R, Mansat-De Mas V, La Starza R, Bastard C, et al. Myeloid cell differentiation arrest by miR -125b-1 in myelodysplastic syndromes and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. J Exp Med. 2008;205(11):2499–506.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, et al. Aberrant microRNA expression pattern in myelodysplastic bone marrow cells. Leukemia Res. 2010;34(9):1169–74.CrossRef Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, et al. Aberrant microRNA expression pattern in myelodysplastic bone marrow cells. Leukemia Res. 2010;34(9):1169–74.CrossRef
26.
Zurück zum Zitat Pons A, Nomdedeu B, Navarro A, Gaya A, Gel B, Diaz T, et al. Hematopoiesis-related microRNA expression in myelodysplastic syndromes. Leuk Lymphoma. 2009;50(11):1854–9.CrossRefPubMed Pons A, Nomdedeu B, Navarro A, Gaya A, Gel B, Diaz T, et al. Hematopoiesis-related microRNA expression in myelodysplastic syndromes. Leuk Lymphoma. 2009;50(11):1854–9.CrossRefPubMed
27.
Zurück zum Zitat McGlinn E, Yekta S, Mansfield JH, Soutscjel J, Bartel DP, Tabin CJ. In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation. Pro Natl Acad Sci USA. 2009; 106(44):18610–5. McGlinn E, Yekta S, Mansfield JH, Soutscjel J, Bartel DP, Tabin CJ. In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation. Pro Natl Acad Sci USA. 2009; 106(44):18610–5.
28.
Zurück zum Zitat Marcucci G, Mrózek K, Radmacher MD, Garzon R, Bloomfield CD. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood. 2011;117(4):1121–9.CrossRefPubMedPubMedCentral Marcucci G, Mrózek K, Radmacher MD, Garzon R, Bloomfield CD. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood. 2011;117(4):1121–9.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Danen-van AA, Kuipers JE, Arentsen-Peters S, Schotte D, de Haas V, Trka J, et al. Differrentially expressed microRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukimia. Pediatr Blood Cancer. 2012;58(5):715–21.CrossRef Danen-van AA, Kuipers JE, Arentsen-Peters S, Schotte D, de Haas V, Trka J, et al. Differrentially expressed microRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukimia. Pediatr Blood Cancer. 2012;58(5):715–21.CrossRef
30.
Zurück zum Zitat Wang Y, Li Z, He C, Wang D, Yuan X, Chen J, et al. MicroRNAs expression signatures are associated with lineage and survival in acute leukemia. Blood Cells Mol Dis. 2010;44(3):191–7.CrossRefPubMedPubMedCentral Wang Y, Li Z, He C, Wang D, Yuan X, Chen J, et al. MicroRNAs expression signatures are associated with lineage and survival in acute leukemia. Blood Cells Mol Dis. 2010;44(3):191–7.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood. 2009;113(14):3314–22.CrossRefPubMedPubMedCentral Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood. 2009;113(14):3314–22.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8.CrossRefPubMedPubMedCentral Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105(30):10513–8.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev. 2009;23(23):2700–4.CrossRefPubMedPubMedCentral Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev. 2009;23(23):2700–4.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852–7.CrossRefPubMedPubMedCentral Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852–7.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Fu CM, Chen ZX, Liu DD, Zhang J, Pan JL, Liang JY. Clonal origin and evolution of myelodysplastic syndromes analyzed by dysplastic morphology and fluorescence in situ hybridization. Int J Hematol. 2015;101(1):58–66.CrossRefPubMed Fu CM, Chen ZX, Liu DD, Zhang J, Pan JL, Liang JY. Clonal origin and evolution of myelodysplastic syndromes analyzed by dysplastic morphology and fluorescence in situ hybridization. Int J Hematol. 2015;101(1):58–66.CrossRefPubMed
Metadaten
Titel
Over-expression of miR-196b-5p is significantly associated with the progression of myelodysplastic syndrome
verfasst von
Jing Wen
Ying Huang
Hongying Li
Xupai Zhang
Peng Cheng
Donghong Deng
Zhigang Peng
Jun Luo
Weihua Zhao
Yongrong Lai
Zhenfang Liu
Publikationsdatum
21.02.2017
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 6/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2201-9

Weitere Artikel der Ausgabe 6/2017

International Journal of Hematology 6/2017 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.