Reduce proliferation of human bone marrow cells from acute myeloblastic leukemia with minimally differentiation by block
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RESEARCH ARTICLE
Reduce proliferation of human bone marrow cells from acute myeloblastic leukemia with minimally differentiation by blocking lncRNA PVT1 A. Ghadiri1 · M. Sharifi1 · V. Mehrzad2 · P. Bagheri1 Received: 29 January 2020 / Accepted: 28 April 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
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. Keywords Acute myeloblastic leukemia · PVT1 · c-Myc · LNA GapmeRs
Introduction
* M. Sharifi [email protected] A. Ghadiri [email protected] V. Mehrzad [email protected] P. Bagheri [email protected] 1
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, 81744‑176 Isfahan, Iran
Department of Internal Medicine, Division of Hematology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2
In the past several years, there has been huge progress in molecular studies by knowing non-coding RNAs (ncRNAs) also known as non-messenger RNA (nmRNA) or functional RNA (fRNA) and their function [1]. ncRNAs thought to be the noise of the transcription system [2]. These non-coding RNAs consist of microRNAs (miRNAs), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNAs), and long non-coding RNA (lncRNAs) [1]. Long non-coding RNAs are which longer than 200 nucleotides in length and like messenger RNAs (mRNA) are transcribed by RNA pol II. lncRNAs get spliced and are capped and usually polyadenylated like mRNAs [1, 3, 4]. lncRNAs can be divided into four groups based on their loci. These four groups are sense, antisense, intronic, and intergenic [5]. They play role in
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