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RETRACTED ARTICLE: Blockage of miR-92a-3p with locked nucleic acid induces apoptosis and prevents cell proliferation in human acute megakaryoblastic leukemia

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A Retraction to this article was published on 13 January 2020

Abstract

MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation of gene expression. In many cancers, up- or downregulation of different miRNAs is reported. In acute myeloid leukemia, upregulation of miR-92a-3p was reported in human in vitro studies. We performed blockage of miR-29a-3p in human acute megakaryoblastic leukemia cell line (M-07e) by using locked nucleic acid (LNA) and cell proliferation; apoptosis and necrosis were assessed. At different time points after LNA-anti-miR92a-3p transfection, miR-92a-3p quantitation was assessed by qRT-real-time PCR, MTT assay and annexin/propidium iodide staining were performed. The data were processed using the ANOVA test. At all three time points, the expression of miR-92a-3p was lower in the LNA-anti-miR group compared with the control groups. Cell viability between LNA-Anti-miR and the control group was statistically significant. Blockage of miR-92a-3p was associated with increment of the ratio of apoptotic cells in the LNA-anti-miR group was higher than the other group. The ratio of necrotic cells in the LNA-antimiR group was higher than the other groups. These assessments indicate that miR-92a-3p blockage can decrease the viability of M-07e cells, which is mainly due to induction of apoptosis and necrosis. Our findings could open up a path to a miRNA based therapeutic approach for treatment of acute megakaryoblastic leukemia.

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References

  1. Ha M, Kim VN . Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15: 509–524.

    Article  CAS  PubMed  Google Scholar 

  2. Lee RC, Feinbaum RL, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75: 843–854.

    Article  CAS  PubMed  Google Scholar 

  3. Drakaki A, Iliopoulos D . MicroRNA gene networks in oncogenesis. Curr Genomics 2009; 10: 35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Taylor DD, Gercel-taylor C . MicroRNA biomarkers. In: US Patent 20150018227, 2015.

  5. Rottiers V, Näär AM . MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol 2012; 13: 239–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hussein K, Büsche G, Muth M, Göhring G, Kreipe H, Bock O . Expression of myelopoiesis-associated microRNA in bone marrow cells of atypical chronic myeloid leukaemia and chronic myelomonocytic leukaemia. Ann Hematol 2011; 90: 307–313.

    Article  CAS  PubMed  Google Scholar 

  7. Farazi T, Hoell J, Morozov P, Tuschl T . MicroRNAs in Human Cancer. In: Schmitz U, Wolkenhauer O, Vera J (eds). MicroRNA Cancer Regulation, vol. 774. Springer: The Netherlands, 2013, pp 1–20.

    Google Scholar 

  8. Geusens B, Strobbe T, Bracke S, Dynoodt P, Sanders N, Gele MV et al. Lipid-mediated gene delivery to the skin. Eur J Pharm Sci 2011; 43: 199–211.

    Article  CAS  PubMed  Google Scholar 

  9. Wang H, Lu H, Yang W, Luo C, Lu S, Zhou Y et al. The influence of statin therapy on circulating microRNA-92a expression in patients with coronary heart disease. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2012; 24: 215.

    PubMed  Google Scholar 

  10. Hammond SM . RNAi, microRNAs, and human disease. Cancer Chemother Pharmacol 2006; 58: 63–68.

    Article  CAS  Google Scholar 

  11. Najafi Z, Sharifi M, Javadi G . Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma. Cancer Gene Ther 2015; 22: 530–535.

    Article  CAS  PubMed  Google Scholar 

  12. Klepin H, Pardee T . Acute Myeloid Leukemia. In: Wedding U, Audisio RA (eds). Management of Hematological Cancer in Older People. Springer: London, 2015, pp 63–83.

    Google Scholar 

  13. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J . Acute Myeloid Leukemia. McGraw-Hill: New York, 2012.

    Google Scholar 

  14. Molina CA, Rodríguez MJR, de Marcos NS, Font P . Acute myeloblastic leukemia. Adv Ther 2011; 28: 10–16.

    Article  PubMed  Google Scholar 

  15. Hamdi FY, Hamdi MN, Hamadi AY, Algehainy NA, Mahzari AM . Role of Different MicroRNAs in Acute Myeloid Leukemia. Int J Genetics Cancer 2015; 1: 3–4.

    Google Scholar 

  16. Ranganathan P, Garzon R . Clinical Implications of MicroRNAs in AML. In: Andreeff M (ed). Targeted Therapy of Acute Myeloid Leukemia. Springer: New York, 2015, pp 699–705.

    Book  Google Scholar 

  17. Zhu Y-D, Wang L, Sun C, Fan L, Zhu D-X, Fang C et al. Distinctive microRNA signature is associated with the diagnosis and prognosis of acute leukemia. Med Oncol 2012; 29: 2323–2331.

    Article  CAS  PubMed  Google Scholar 

  18. Benetatos L, Vartholomatos G . MicroRNAs mark in the MLL-rearranged leukemia. Ann Hematol 2013; 92: 1439–1450.

    Article  CAS  PubMed  Google Scholar 

  19. Kandi R, Undi R, Gutti RK . MiR-125b regulates cell proliferation and survival in neonatal megakaryocytes. Ann Hematol 2014; 93: 1065–1066.

    Article  PubMed  Google Scholar 

  20. Testa U, Pelosi E . MicroRNAs expressed in hematopoietic stem/progenitor cells are deregulated in acute myeloid leukemias. Leukemia & lymphoma 2015; 56: 1466–1474.

    Article  CAS  Google Scholar 

  21. Ohyashiki JH, Umezu T, Kobayashi C, Hamamura RS, Tanaka M, Kuroda M et al. Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in vivo assessment of cell to plasma ratio of miR-92a. BMC Res Notes 2010; 3: 347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS One 2009; 4: e5532.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Manni I, Artuso S, Careccia S, Rizzo MG, Baserga R, Piaggio G et al. The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEB J 2009; 23: 3957–3966.

    Article  CAS  PubMed  Google Scholar 

  24. Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A et al. The miR-17∼ 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci USA 2009; 106: 2812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yoshizawa S, Ohyashiki J, Ohyashiki M, Umezu T, Suzuki K, Inagaki A et al. Downregulated plasma miR-92a levels have clinical impact on multiple myeloma and related disorders. Blood Cancer J 2012; 2: e53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Braoudaki M, Lambrou GI . MicroRNAs in pediatric central nervous system embryonal neoplasms: the known unknown. J Hematol Oncol 2015; 8: 6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Ramzy I, Hasaballah M, Marzaban R, Shaker O, Soliman ZA . Evaluation of microRNAs-29a, 92a and 145 in colorectal carcinoma as candidate diagnostic markers: an Egyptian pilot study. Clin Res Hepatol Gastroenterol 2015; 39: 508–515.

    Article  CAS  PubMed  Google Scholar 

  28. Zhu L, Chen H, Zhou D, Li D, Bai R, Zheng S et al. MicroRNA-9 up-regulation is involved in colorectal cancer metastasis via promoting cell motility. Med Oncol 2012; 29: 1037–1043.

    Article  CAS  PubMed  Google Scholar 

  29. Stenvang J, Petri A, Lindow M, Obad S, Kauppinen S . Inhibition of microRNA function by antimiR oligonucleotides. Silence 2012; 3: 1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ørom UA, Kauppinen S, Lund AH . LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 2006; 372: 137–141.

    Article  PubMed  CAS  Google Scholar 

  31. Stoffel M, Poy MN, Tuschl TH . MicroRNA and methods for inhibiting same. Google Patents, 2014..

  32. Kadia T, Ravandi F . Induction Therapy in Acute Myeloid Leukemia. In: Cancer Consult: Expertise for Clinical Practice. John Wiley & Sons, Ltd, 2014, pp 58–66.

  33. Iorio MV, Croce CM . MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 2012; 4: 143–159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cheng CJ, Engelman DM, Saltzman M, Slack FJ . Targeting the tumor microenvironment with antimiRs that exploit oncomiR addiction in lymphoma. Cancer Res 2014; 74: 974–974.

    Article  CAS  Google Scholar 

  35. Sharifi M, Salehi R, Gheisari Y, Kazemi M . Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression. Mol Biol Rep 2014; 41: 2799–2808.

    Article  CAS  PubMed  Google Scholar 

  36. Zhou C, Shen L, Mao L, Wang B, Li Y, Yu H . miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7. Biochem Biophys Res Commun 458: 63–69 2015.

    Article  CAS  PubMed  Google Scholar 

  37. Li M, Guan X, Sun Y, Mi J, Shu X, Liu F et al. miR-92a family and their target genes in tumorigenesis and metastasis. Exp Cell Res 2014; 323: 1–6.

    Article  CAS  PubMed  Google Scholar 

  38. Al-Nakhle H, Burns PA, Cummings M, Hanby AM, Hughes TA, Satheesha S et al. Estrogen receptor β1 expression is regulated by miR-92 in breast cancer. Cancer Res 2010; 70: 4778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Iorio MV, Croce CM . MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 2012; 4: 143–159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sharifi M, Salehi R, Gheisari Y, Kazemi M . Inhibition of MicroRNA miR-92a inhibits cell proliferation in human acute promyelocytic leukemia. Turk J Haematol 2013; 30: 157.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Shipley JL, Butera JN . Acute myelogenous leukemia. Exp Haematol 2009; 37: 649–658.

    Article  CAS  Google Scholar 

  42. Gu J, Zhu X, Li Y, Dong D, Yao J, Lin C et al. miRNA-21 regulates arsenic-induced anti-leukemia activity in myelogenous cell lines. Med Oncol 2011; 28: 211–218.

    Article  CAS  PubMed  Google Scholar 

  43. Li Y, Zhu X, Gu J, Dong D, Yao J, Lin C et al. Anti‐miR‐21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis. Cancer Sci 2010; 101: 948–954.

    Article  CAS  PubMed  Google Scholar 

  44. Rashidi A, Fisher SI . Acute megakaryoblastic leukemia. Blood 2013; 122: 2537–2537.

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was conducted with the financial support of the Isfahan University of Medical Sciences (IRAN).

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Authors and Affiliations

  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    M Sharifi & R Salehi

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  1. M Sharifi
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Correspondence to M Sharifi.

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The Editor-in-Chief has retracted this article because it overlaps significantly with three previous articles by the same author group. Both authors disagree with this retraction.

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Sharifi, M., Salehi, R. RETRACTED ARTICLE: Blockage of miR-92a-3p with locked nucleic acid induces apoptosis and prevents cell proliferation in human acute megakaryoblastic leukemia. Cancer Gene Ther 23, 29–35 (2016). https://doi.org/10.1038/cgt.2015.63

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