Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia

被引:116
作者
Fathullahzadeh, S. [1 ]
Mirzaei, H. [2 ]
Honardoost, M. A. [3 ]
Sahebkar, A. [4 ]
Salehi, M. [5 ]
机构
[1] Islamic Azad Univ, Ashkezar Branch, Med Biotechnol Res Ctr, Yazd, Iran
[2] Mashhad Univ Med Sci, Sch Med, Dept Med Biotechnol, Mashhad, Iran
[3] Univ Isfahan, Fac Sci, Dept Biol, Div Cell & Mol Biol, Esfahan, Iran
[4] Mashhad Univ Med Sci, Biotechnol Res Ctr, Mashhad, Iran
[5] Isfahan Univ Med Sci, Sch Med, Dept Genet & Mol Biol, Esfahan 9177948564, Iran
关键词
P53; DYSFUNCTION; CELL; EXPRESSION; GENE; METASTASIS; SIGNATURES; MIR-192; DISEASE;
D O I
10.1038/cgt.2016.34
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR-192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months. Using real-time PCR method, expression of miR-192 was analyzed in peripheral blood mononuclear cells (PBMCs) of CLL patients in comparison with healthy subjects. In silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-192 in DAVID database to explore possible role of miR-192 in some pathways. The expression of miR-192 was found to be significantly reduced (similar to 2.5-folds) in CLL patients compared with healthy subjects (P=0.002). In silico molecular signaling pathway enrichment analysis detected cell indicated signaling pathway as one of the most statistically relevant pathway with miR-192 targetome. Our findings showed that miR-192 could be a biomarker for early diagnosis of CLL.
引用
收藏
页码:327 / 332
页数:6
相关论文
共 31 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Wnt4 inhibits β-catenin/TCF signalling by redirecting β-catenin to the cell membrane [J].
Bernard, Pascal ;
Fleming, Alice ;
Lacombe, Arnaud ;
Harley, Vincent R. ;
Vilain, Eric .
BIOLOGY OF THE CELL, 2008, 100 (03) :167-177
[3]   p53-Responsive MicroRNAs 192 and 215 Are Capable of Inducing Cell Cycle Arrest [J].
Braun, Christian J. ;
Zhang, Xin ;
Savelyeva, Irina ;
Wolff, Sonja ;
Moll, Ute M. ;
Schepeler, Troels ;
Orntoft, Torben F. ;
Andersen, Claus L. ;
Dobbelstein, Matthias .
CANCER RESEARCH, 2008, 68 (24) :10094-10104
[4]   MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias [J].
Calin, GA ;
Liu, CG ;
Sevignani, C ;
Ferracin, M ;
Felli, N ;
Dumitru, CD ;
Shimizu, M ;
Cimmino, A ;
Zupo, S ;
Dono, M ;
Dell'Aquila, ML ;
Alder, H ;
Rassenti, L ;
Kipps, TJ ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) :11755-11760
[5]   Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer [J].
Chen, Qingjuan ;
Ge, Xiaojun ;
Zhang, Yuchen ;
Xia, Hongwei ;
Yuan, Dandan ;
Tang, Qiulin ;
Chen, Liang ;
Pang, Xiaohui ;
Leng, Weibing ;
Bi, Feng .
ONCOLOGY REPORTS, 2014, 31 (04) :1863-1870
[6]   Mechanisms of disease: Chronic lymphocytic leukemia [J].
Chiorazzi, N ;
Rai, KR ;
Ferrarini, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (08) :804-815
[7]   Cell cycle progression of chronic lymphocytic leukemia cells is controlled by cyclin D2, cyclin D3, cyclin-dependent kinase (cdk) 4 and the cdk inhibitor p27 [J].
Decker, T ;
Schneller, F ;
Hipp, S ;
Miething, C ;
Jahn, T ;
Duyster, J ;
Peschel, C .
LEUKEMIA, 2002, 16 (03) :327-334
[8]   MicroRNA signatures in B-cell lymphomas [J].
Di Lisio, L. ;
Sanchez-Beato, M. ;
Gomez-Lopez, G. ;
Rodriguez, M. E. ;
Montes-Moreno, S. ;
Mollejo, M. ;
Menarguez, J. ;
Martinez, M. A. ;
Alves, F. J. ;
Pisano, D. G. ;
Piris, M. A. ;
Martinez, N. .
BLOOD CANCER JOURNAL, 2012, 2 :e57-e57
[9]   MicroRNAs in B cell development and malignancy [J].
Fernando, Thilini R. ;
Rodriguez-Malave, Norma I. ;
Rao, Dinesh S. .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2012, 5
[10]   MicroRNA-192 suppresses liver metastasis of colon cancer [J].
Geng, L. ;
Chaudhuri, A. ;
Talmon, G. ;
Wisecarver, J. L. ;
Are, C. ;
Brattain, M. ;
Wang, J. .
ONCOGENE, 2014, 33 (46) :5332-5340