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Molecular Biology Reports

, Volume 41, Issue 5, pp 2799–2808 | Cite as

Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression

  • Mohammadreza Sharifi
  • Rasoul Salehi
  • Yousof Gheisari
  • Mohammad Kazemi
Article

Abstract

MicroRNAs (miRNAs) are endogenous non-coding RNAs, 19–25 nucleotides in length involved in post-transcriptional regulation of gene expression of great majority of the human protein coding genes. Different aspects of cellular activities like cell growth, proliferation, and differentiation are regulated by miRNAs through their interaction with particular RNA species. In many tumors up or down-regulation of different miRNAs has been reported. Human miR-17-92 gene cluster is located on 13q31.3, rooming several miRNAs including miR-17-5p, miR-17-3p, miR-18, miR-19a, miR-20a and miR-92a. Amplification or overexpression of this cluster has been reported in acute myeloid leukemia, acute lymphoblastic leukemia and several other cancer types. Here, we performed inhibition of miR-92a in an acute promyelocytic leukemia (APL) cell line (HL-60) using locked nucleic acid (LNA) antagomir. In different time points after LNA-anti-miR92a transfection, MTT assay and annexin/propidium iodide staining were performed. These assessments indicate that miR-92a inhibition can extensively decrease the viability of these cells which is mainly due to induction of apoptosis. Western blot analysis of p63 protein also revealed that miR-92a inhibition resulted in p63 expression, hence activation of cellular pathways which are normally controlled by p63 protein are retrieved. These findings could open up a path to the miRNAs based therapeutic approach for treatment of APL.

Keywords

MicroRNA miR-92a p63 Acute promyelocytic leukemia Locked nucleic acid 

Notes

Acknowledgments

This study was conducted with financial support of Isfahan University of Medical Sciences (IRAN) with grant number 390255.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Mohammadreza Sharifi
    • 1
  • Rasoul Salehi
    • 1
  • Yousof Gheisari
    • 1
  • Mohammad Kazemi
    • 1
  1. 1.Department of Genetics and Molecular Biology, School of MedicineIsfahan University of Medical SciencesIsfahanIran

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