Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia

  • Mahtab Sayadi Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
  • Soheila Ajdary Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
  • Fatemeh Nadali Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
  • Shahrbano Rostami Department of Hematology, Hematology and Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Mahdi Edalati Fahtabad Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Acute lymphoblastic leukemia, apoptosis, cell cycle, miroRNA-192, ALL, P53, BAX, CASP3, BCL-2

Abstract

Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced expression of microRNA-192 (miR-192) has been detected in many cancers. In this study, we investigated the role of miR-192 in cell proliferation and cell cycle control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL). Cell cycle analysis by DNA content using propidium iodide staining and cell apoptosis analysis using Annexin V assay were carried out. Cell proliferation changes were monitored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene expression were determined by quantitative reverse transcription PCR. Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells. After 72 and 96 hours of transduction, apoptosis was significantly increased in the cells transduced with miR-192-overexpressing virus compared with control cells. The expression of P53, BAX, and CASP3 increased after 48 hours of transduction in miR-192-overexpressing cells, but no change was observed in BCL-2 expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the cells overexpressing miR-192 compared with controls. The results of our study suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells.

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Author Biographies

Mahtab Sayadi, Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
Department of Hematology
Soheila Ajdary, Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
Department of Immunology
Fatemeh Nadali, Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
Department of Hematology
Shahrbano Rostami, Department of Hematology, Hematology and Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
Department of Hematology
Mahdi Edalati Fahtabad, Department of Hematology, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran
Department of Hematology

References

Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004;116(2):281-97. https://doi.org/10.1016/S0092-8674(04)00045-5.

Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009;136(2):215-33. https://doi.org/10.1016/j.cell.2009.01.002.

Ruvkun G. Clarifications on miRNA and cancer. Science 2006;311(5757):36-7. https://doi.org/10.1126/science.311.5757.36d.

Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol 2007;302(1):1-12. https://doi.org/10.1016/j.ydbio.2006.08.028.

Xi Y, Shalgi R, Fodstad O, Pilpel Y, Ju J. Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clin Cancer Res 2006;12(7 Pt 1):2014-24. https://doi.org/10.1158/1078-0432.CCR-05-1853.

Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP. Vertebrate microRNA genes. Science 2003;299(5612):1540. https://doi.org/10.1126/science.1080372.

Hino K, Tsuchiya K, Fukao T, Kiga K, Okamoto R, Kanai T, et al. Inducible expression of microRNA-194 is regulated by HNF-1alpha during intestinal epithelial cell differentiation. RNA 2008;14(7):1433-42. https://doi.org/10.1261/rna.810208.

Tan Y, Ge G, Pan T, Wen D, Chen L, Yu X, et al. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus. PLoS One 2014;9(9):e107986. https://doi.org/10.1371/journal.pone.0107986.

Feinberg-Gorenshtein G, Guedj A, Shichrur K, Jeison M, Luria D, Kodman Y, et al. MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma. PLoS One 2013;8(11):e78713. https://doi.org/10.1371/journal.pone.0078713.

Jin Z, Selaru FM, Cheng Y, Kan T, Agarwal R, Mori Y, et al. MicroRNA-192 and -215 are upregulated in human gastric cancer in vivo and suppress ALCAM expression in vitro. Oncogene 2011;30(13):1577-85. https://doi.org/10.1038/onc.2010.534.

Song B, Wang Y, Kudo K, Gavin EJ, Xi Y, Ju J. miR-192 regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit. Clin Cancer Res 2008;14(24):8080-6. https://doi.org/10.1158/1078-0432.CCR-08-1422.

Schotte D, De Menezes RX, Akbari Moqadam F, Khankahdani LM, Lange-Turenhout E, Chen C, et al. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica 2011;96(5):703-11. https://doi.org/10.3324/haematol.2010.026138.

Muller PA, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013;15(1):2-8. https://doi.org/10.1038/ncb2641.

Surget S, Khoury MP, Bourdon JC. Uncovering the role of p53 splice variants in human malignancy: A clinical perspective. Onco Targets Ther 2013;7:57-68. https://doi.org/10.2147/OTT.S53876.

Tudzarova S, Mulholland P, Dey A, Stoeber K, Okorokov AL, Williams GH, et al. p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress. Cell Cycle 2016;15(21):2958-72. https://doi.org/10.1080/15384101.2016.1231281.

Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene 2001;20(15):1803-15. https://doi.org/10.1038/sj.onc.1204252.

Khella HW, Bakhet M, Allo G, Jewett MA, Girgis AH, Latif A, et al. miR-192, miR-194 and miR-215: A convergent microRNA network suppressing tumor progression in renal cell carcinoma. Carcinogenesis 2013;34(10):2231-9. https://doi.org/10.1093/carcin/bgt184.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435(7043):834-8. https://doi.org/10.1038/nature03702.

Schwartz D, Almog N, Peled A, Goldfinger N, Rotter V. Role of wild type p53 in the G2 phase: Regulation of the gamma-irradiation-induced delay and DNA repair. Oncogene 1997;15(21):2597-607. https://doi.org/10.1038/sj.onc.1201436.

Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74(4):609-19. https://doi.org/10.1016/0092-8674(93)90509-O.

Weng C, Li Y, Xu D, Shi Y, Tang H. Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells. J Biol Chem 2005;280(11):10491-500. https://doi.org/10.1074/jbc.M412819200.

Jin Y, Lu J, Wen J, Shen Y, Wen X. Regulation of growth of human bladder cancer by miR-192.Tumour Biol 2015;36(5):3791-7. DOI: 10.1007/s13277-014-3020-8.

Published
2017-08-20
How to Cite
1.
Sayadi M, Ajdary S, Nadali F, Rostami S, Edalati Fahtabad M. Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia. Bosn J of Basic Med Sci [Internet]. 2017Aug.20 [cited 2019Nov.13];17(3):248-54. Available from: http://bjbms.org/ojs/index.php/bjbms/article/view/1921
Section
Molecular Biology