Expression analysis of mir-17-5p, mir-20a and let-7a microRNAs and their target proteins in CD34+ bone marrow cells of patients with myelodysplastic syndromes

被引:30
作者
Vasilatou, Diamantina [1 ,2 ]
Papageorgiou, Sotirios G. [1 ,2 ]
Kontsioti, Frieda [1 ,2 ]
Kontos, Christos K. [3 ,4 ]
Tsiotra, Panayiota [1 ,2 ]
Mpakou, Vassiliki [1 ,2 ]
Pavlou, Maria-Angeliki S. [4 ]
Economopoulou, Christina [1 ,2 ]
Dimitriadis, George [1 ,2 ]
Dervenoulas, John [1 ,2 ]
Pappa, Vasiliki [1 ,2 ]
机构
[1] Univ Athens, Sch Med, Attikon Univ Gen Hosp, Dept Internal Med 2, Athens 12462, Greece
[2] Univ Athens, Sch Med, Attikon Univ Gen Hosp, Res Inst, Athens 12462, Greece
[3] Univ Athens, Dept Biochem & Mol Biol, Athens 12462, Greece
[4] Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Lab Signal Mediated Gene Express, Athens, Greece
关键词
MDS; MicroRNAs; Let-7a; Mir-17-5p; Mir-20a; ACUTE MYELOID-LEUKEMIA; E2F-DEPENDENT APOPTOSIS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; E2F1; CANCER; RAS; ONCOGENE; SURVIVAL; GROWTH;
D O I
10.1016/j.leukres.2012.11.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mir-17-5p and mir-20a, members of the mir-17-92 family, down-regulate E2F1, which is over-expressed in myelodysplastic syndromes (MDS). Moreover, let-7a down-regulates KRAS, which is aberrantly expressed in MDS. We evaluated the expression of the aforementioned microRNAs in CD34+ cells of 43 MDS patients using real-time PCR and their target proteins (E2F1, MYC, BCL2, CCND1, and KRAS) by Western blot. Mir-17-5p and mir-20a were under expressed in high risk MDS patients, compared to low risk MDS patients. Similarly, let-7a was under expressed in patients with intermediate or high-risk karyotype. Interestingly, there was an inverse correlation between microRNA and the expression levels of their targets. Importantly, mir-17-5p and mir-20a constitute favorable prognostic factors in MDS, since their expression was associated with increased overall survival of MDS patients. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:251 / 258
页数:8
相关论文
共 49 条
[1]   let-7 microRNA functions as a potential growth suppressor in human colon cancer cells [J].
Akao, Yukihiro ;
Nakagawa, Yoshihito ;
Naoe, Tomoki .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2006, 29 (05) :903-906
[2]   X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization [J].
Camp, RL ;
Dolled-Filhart, M ;
Rimm, DL .
CLINICAL CANCER RESEARCH, 2004, 10 (21) :7252-7259
[3]   Transcriptional regulation of AKT activation by E2F [J].
Chaussepied, M ;
Ginsberg, D .
MOLECULAR CELL, 2004, 16 (05) :831-837
[4]   miR-17-92 cluster microRNAs confers tumorigenicity in multiple myeloma [J].
Chen, Lijuan ;
Li, Chunming ;
Zhang, Run ;
Gao, Xiao ;
Qu, Xiaoyan ;
Zhao, Min ;
Qiao, Chun ;
Xu, Jiaren ;
Li, Jianyong .
CANCER LETTERS, 2011, 309 (01) :62-70
[5]   The molecular pathogenesis of myelodysplastic syndromes [J].
Davids, Matthew S. ;
Steensma, David P. .
CANCER BIOLOGY & THERAPY, 2010, 10 (04) :309-319
[6]   Diagnostic microRNAs in myelodysplastic syndrome [J].
Erdogan, Begum ;
Facey, Crystal ;
Qualtieri, Julianne ;
Tedesco, Jason ;
Rinker, Elizabeth ;
Isett, R. Benjamin ;
Tobias, John ;
Baldwin, Donald A. ;
Thompson, James E. ;
Carroll, Martin ;
Kim, Annette S. .
EXPERIMENTAL HEMATOLOGY, 2011, 39 (09) :915-926
[7]   The let-7 microRNA reduces tumor growth in mouse models of lung cancer [J].
Esquela-Kerscher, Aurora ;
Trang, Phong ;
Wiggins, Jason F. ;
Patrawala, Lubna ;
Cheng, Angie ;
Ford, Lance ;
Weidhaas, Joanne B. ;
Brown, David ;
Bader, Andreas G. ;
Slack, Frank J. .
CELL CYCLE, 2008, 7 (06) :759-764
[8]   MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation [J].
Fontana, Laura ;
Pelosi, Elvira ;
Greco, Paolo ;
Racanicchi, Serena ;
Testa, Ugo ;
Liuzzi, Francesca ;
Croce, Carlo M. ;
Brunetti, Ercole ;
Grignani, Francesco ;
Peschle, Cesare .
NATURE CELL BIOLOGY, 2007, 9 (07) :775-U90
[9]   MicroRNA fingerprints during human megakaryocytopoiesis [J].
Garzon, R ;
Pichiorri, F ;
Palumbo, T ;
Iuliano, R ;
Cimmino, A ;
Aqeilan, R ;
Volinia, S ;
Bhatt, D ;
Alder, H ;
Marcucci, G ;
Calin, GA ;
Liu, CG ;
Bloomfield, CD ;
Andreeff, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (13) :5078-5083
[10]   CD34+hematopoietic stem-progenitor cell microRNA expression and function: A circuit diagram of differentiation control [J].
Georgantas, Robert W., III ;
Hildreth, Richard ;
Morisot, Sebastien ;
Alder, Jonathan ;
Liu, Chang-gong ;
Heimfeld, Shelly ;
Calin, George A. ;
Croce, Carlo M. ;
Civin, Curt I. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (08) :2750-2755