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Reduce proliferation of human bone marrow cells from acute myeloblastic leukemia with minimally differentiation by blocking lncRNA PVT1

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Abstract

Purpose

Acute myeloblastic leukemia with minimally differentiation (AML-M0) is a subtype of acute leukemia with poor prognosis. The recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in different cellular processes, such as cell cycle control and proliferation. Plasmacytoma variant translocation 1 (PVT1) is one of those lncRNAs that is significantly upregulated in AML. LncRNAs could be downregulated or blocked by locked nucleic acids (LNA) which are oligonucleotide strands.

Methods

In this study, lncRNA PVT1 was blocked by antisense LNA GapmeRs in human bone marrow cancerous blast cells. Cells were transfected with PVT1 antisense LNA GapmeRs at 24, 48, and 72 h post-transfection. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was accomplished to evaluate the PVT1 and c-Myc expression. Cell viability was evaluated by MTT assay, and apoptosis and necrosis were assessed by Annexin V/propidium iodide staining assay.

Results

The results of this study indicated that the downregulation of PVT1 in blast cells could induce apoptosis, and necrosis and reduce cell viability. The expression of c-Myc was downregulated by blockage of PVT1 and it shows that the expression of these two genes are correlated.

Conclusion

The findings declare that inhibition of PVT1 could be a new target in the treatment of AML-M0 and help to approach more to treatments with fewer side effects.

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Acknowledgements

This study was conducted with the financial support of Isfahan University of Medical Sciences (IRAN) with Grant Number 396877.

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Authors and Affiliations

  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, 81744-176, Isfahan, Iran

    A. Ghadiri, M. Sharifi & P. Bagheri

  2. Department of Internal Medicine, Division of Hematology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    V. Mehrzad

Authors
  1. A. Ghadiri
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  2. M. Sharifi
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  3. V. Mehrzad
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  4. P. Bagheri
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Correspondence to M. Sharifi.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the local ethics committee of Isfahan University of Medical Sciences (IRAN) and the study has been approved by the appropriate institutional and/or national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ghadiri, A., Sharifi, M., Mehrzad, V. et al. Reduce proliferation of human bone marrow cells from acute myeloblastic leukemia with minimally differentiation by blocking lncRNA PVT1. Clin Transl Oncol 22, 2103–2110 (2020). https://doi.org/10.1007/s12094-020-02360-4

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  • DOI: https://doi.org/10.1007/s12094-020-02360-4

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