|Table of Contents|

Study on the expression and function of DICER1 in leukemic cell lines

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2014 01
Page:
22-0026
Research Field:
Publishing date:

Info

Title:
Study on the expression and function of DICER1 in leukemic cell lines
Author(s):
Bai YingLiu YanqinWang JigangLiu JinghuaLi ShanshanZhou Fan
Department of Hematology,General Hospital of Shenyang Military Region,Liaoning Shenyang 110056,China.
Keywords:
leukemiaDICER1HL-60 cellKG-1 cellproliferationapoptosis
PACS:
R730.21;R733.71
DOI:
10.3969/j.issn.1672-4992.2014.01.07
Abstract:
Objective:To assess the DICER1 expression levels in leukemic cell lines HL-60 and KG-1,and further investigate the effects of silencing DICER1 on cell proliferation and apoptosis in leukemia cell lines.The findings will provide a theoretical basis to reveal the role of DICER1 in the pathogenesis of leukemia.Methods:The mRNA and protein levels of DICER1 in leukemic cell lines HL-60 and KG-1 were detected by real time-PCR and Western blot.Human leukemia HL-60 and KG-1 cells were transfected with an DICER1-shRNA expressing vector by LipofectamineTMLTX.Real-time quantitative PCR and Western blot confirmed DICER1 knockdown in both cell lines.Cell proliferation affected by DICER1 interference was assessed using a standard CCK-8 assay.Cell apoptosis was assayed by flow cytometry.Results:DICER1 expression in leukemia cell lines HL-60 and KG-1 was significantly increased both at the mRNA and protein levels,compared with HEK cells(P<0.05).The level of DICER1 mRNA and protein was significantly decreased in both cell lines 5 days following transfection with DICER1-shRNA(P<0.05).Cell proliferation experiments revealed that DICER1 silencing inhibited cell proliferation of HL-60 and KG-1 cells(P<0.05).Flow cytometry analysis demonstrated that silencing of DICER1 significantly induced apoptosis compared to the controls(P<0.01).Conclusions:DICER1 expression level was high in leukemic cell lines HL-60 and KG-1,which may induce leukemia cell proliferation and inhibit apoptosis.

References:

[1]Carmell MA,Hannon GJ.RNase III enzymes and the initiation of gene silencing[J].Nat Struct Mol Biol,2004,11:214-218.
[2]Merritt WM,Bar-Eli M,Sood AK.The dicey role of Dicer:implications for RNAi therapy[J].Cancer Res,2010,70:2571-2574.
[3]He S,Zhang D,Cheng F,et al.Applications of RNA interference in cancer therapeutics as a powerful tool for suppressing gene expression[J].Mol Biol Rep,2009,36:2153-2163.
[4]Takeshita F,Ochiya T.Therapeutic potential of RNA interference against cancer[J].Cancer Sci,2006,97:689-696.
[5]Takahashi Y,Nishikawa M,Takakura Y.In vivo siRNA delivery to tumor cells and its application to cancer gene therapy[J].Yakugaku Zasshi,2007,127:1525-1531.
[6]Bernstein E,Caudy AA,Hammond SM,et al.Role for a bidentate ribonuclease in the initiation step of RNA interference[J].Nature,2001,409(6818):363-366.
[7]Lee YS,Nakahara K,Pham JW,et al.Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways[J].Cell,2004,117:69-81.
[8]Zighelboim I,Reinhart AJ,Gao F,et al.DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma[J].Cancer,2010,117:1446-1453.
[9]William M,Merritt MD,Yvonne G,et al.DICER,Drosha,and Outcomes in patients with ovarian cancer[J].N Engl J Med,2008,359:2641-2650.
[10]Grelier G,Voirin N,Ay AS,et al.Prognostic value of DICER expression in human breast cancers and association with the mesenchymal phenotype[J].Br J Cancer,2009,101:673-683.
[11]Chiosea S,Jelezcova E,Chandran U,et al.Up-regulation of DICER,a component of the microRNA machinery,in prostate adenocarcinoma[J].Am J Pathol,2006,169:1812-1820.
[12]Papachristou DJ,Korpetinou A,Giannopoulou E,et al.Expression of the ribonucleases Drosha,Dicer,and Ago2 in colorectal carcinomas[J].Virchows Arch,2011,459:431-440.
[13]Chiosea S,Jelezcova E,Chandran U,et al.Overexpression of Dicer in precursor lesions of lung adenocarcinoma[J].Cancer Res,2007,67:2345-2350.
[14]Karube Y,Tanaka H,Osada H,et al.Reduced expression of Dicer associated with poor prognosis in lung cancer patients[J].Cancer Sci,2005,96(2):111-115.
[15]Slade I,Bacchelli C,Davies H,et al.DICER1 syndrome:clarifying the diagnosis,clinical features and management implications of a pleiotropic tumour predisposition syndrome[J].J Med Genet,2011,48:273-278.
[16]Raaijmakers MH,Mukherjee S,Guo S,et al.Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia[J].Nature,2010,464:852-857.
[17]Zhu DX,Fan L,Lu RN,et al.Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia[J].Cancer Sci,2012,12:1349-7006.
[18]Zhou YM,Chen L,Barlogie B,et al.High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2[J].Proc Natl Acad Sci USA,2010,107:7904-7809.
[19]Kawase-Koga Y,Low R,Otaegi G,et al.RNAase-III enzyme Dicer maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells[J].J Cell Sci,2010,123:586-594.

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Last Update: 2013-12-03