Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor

被引:7
作者
Lin, Xiao-Cong [1 ]
Xu, Yong [2 ]
Sun, Guo-Ping [2 ]
Wen, Jin-Li [3 ]
Li, Ning [4 ]
Zhang, Yu-Ming [4 ]
Yang, Zhi-Gang [4 ]
Zhang, Hai-Tao [1 ]
Dai, Yong [3 ]
机构
[1] Guangdong Med Univ, Inst Biochem & Mol Biol, Zhanjiang 524023, Guangdong, Peoples R China
[2] Shenzhen Pingshan Peoples Hosp, Shenzhen 518118, Guangdong, Peoples R China
[3] Shenzhen Peoples Hosp, Clin Med Res Ctr, 1017 Dongmen North Rd, Shenzhen 518020, Guangdong, Peoples R China
[4] Guangdong Med Univ, Affiliated Hosp, Dept Hematol, Zhanjiang 524001, Guangdong, Peoples R China
关键词
acute myeloid leukemia; microRNA; transcription factor; sequencing; microarray; C-MYC; EXPRESSION PROFILES; POOR-PROGNOSIS; UP-REGULATION; C/EBP-ALPHA; KAPPA-B; CANCER; PATHOGENESIS; GENE; KINASE;
D O I
10.3892/ijo.2016.3489
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Acute myeloid leukemia (AML) is a heterogenic hematological malignancy with pathogenesis that has yet to be elucidated. MicroRNAs (miRNAs) and transcription factors (TFs) are two major regulators of gene expression, which may play important roles in the etiology of AML. However, the global regulation of gene expression in AML, involving miRNAs and TFs, still remains elusive. To characterize the global role of miRNAs and TFs in AML pathogenesis, large scale expression profiling of miRNA and TF was performed using miRNA sequencing and TF array technology, respectively, and validated by qPCR. In the present study, 308 miRNAs and 84 TFs were identified to be differentially expressed (fold-change-2.0) in AML samples relative to their controls. After integrating the expression profiling data into bioinformatic analysis, we identified 1,462 miRNA-gene pairs, 982 TF-gene pairs and 296 TF-miRNA pairs. By merging these regulatory relations together, we constructed a comprehensive AML-specific miRNA-TF regulatory network. In this network, we identified 22 hub miRNAs and 11 hub TFs. KEGG pathway analysis showed that the network nodes were significantly enriched in 33 different pathways, of which the AML pathway was the most significant. After analyzing the topology of the subnetwork, we propose that TCF3 was a potential key regulator in this regulatory network. In conclusion, this is the first study perform on global expression profiling of miRNAs and TFs relating to AML. These results may enhance our understanding of the molecular mechanisms underlying AML and provide potential targets for future therapeutics.
引用
收藏
页码:2367 / 2380
页数:14
相关论文
共 63 条
  • [1] Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia
    Abdel-Wahab, Omar
    Levine, Ross L.
    [J]. BLOOD, 2013, 121 (18) : 3563 - 3572
  • [2] miR-15a and miR-16-1 in cancer: discovery, function and future perspectives
    Aqeilan, R. I.
    Calin, G. A.
    Croce, C. M.
    [J]. CELL DEATH AND DIFFERENTIATION, 2010, 17 (02) : 215 - 220
  • [3] Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells
    Aurelius, Johan
    Martner, Anna
    Brune, Mats
    Palmqvist, Lars
    Hansson, Markus
    Hellstrand, Kristoffer
    Thoren, Fredrik B.
    [J]. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (12): : 1904 - 1908
  • [4] Aberrant microRNA expression and its implications in the pathogenesis of leukemias
    Babashah, Sadegh
    Sadeghizadeh, Majid
    Tavirani, Mostafa Rezaei
    Farivar, Shirin
    Soleimani, Masoud
    [J]. CELLULAR ONCOLOGY, 2012, 35 (05) : 317 - 334
  • [5] Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia
    Bai, Jin
    Guo, Aiping
    Hong, Ze
    Kuai, Wenxia
    [J]. ONCOTARGETS AND THERAPY, 2012, 5 : 213 - 219
  • [6] Direct and indirect targeting of MYC to treat acute myeloid leukemia
    Brondfield, Sam
    Umesh, Sushma
    Corella, Alexandra
    Zuber, Johannes
    Rappaport, Amy R.
    Gaillard, Coline
    Lowe, Scott W.
    Goga, Andrei
    Kogan, Scott C.
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2015, 76 (01) : 35 - 46
  • [7] Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors
    Burger, Matthew T.
    Han, Wooseok
    Lan, Jiong
    Nishiguchi, Gisele
    Bellamacina, Cornelia
    Lindval, Mika
    Atallah, Gordana
    Ding, Yu
    Mathur, Michelle
    McBride, Chris
    Beans, Elizabeth L.
    Muller, Kristine
    Tamez, Victoriano
    Zhang, Yanchen
    Huh, Kay
    Feucht, Paul
    Zavorotinskaya, Tatiana
    Dai, Yumin
    Holash, Jocelyn
    Castillo, Joseph
    Langowski, John
    Wang, Yingyun
    Chen, Min Y.
    Garcia, Pablo D.
    [J]. ACS MEDICINAL CHEMISTRY LETTERS, 2013, 4 (12): : 1193 - 1197
  • [8] Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A
    Chaudhuri, Aadel A.
    So, Alex Yick-Lun
    Mehta, Arnav
    Minisandram, Aarathi
    Sinha, Nikita
    Jonsson, Vanessa D.
    Rao, Dinesh S.
    O'Connell, Ryan M.
    Baltimore, David
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (11) : 4233 - 4238
  • [9] Construction and Analysis of an Integrated Regulatory Network Derived from High-Throughput Sequencing Data
    Cheng, Chao
    Yan, Koon-Kiu
    Hwang, Woochang
    Qian, Jiang
    Bhardwaj, Nitin
    Rozowsky, Joel
    Lu, Zhi John
    Niu, Wei
    Alves, Pedro
    Kato, Masaomi
    Snyder, Michael
    Gerstein, Mark
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2011, 7 (11)
  • [10] Epigenetic inactivation of INK4/CDK/RB cell cycle pathway in acute leukemias
    Chim, CS
    Wong, ASY
    Kwong, YL
    [J]. ANNALS OF HEMATOLOGY, 2003, 82 (12) : 738 - 742