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.
Clin Transl Oncol. 2020 Nov;22(11):2103-2110. doi: 10.1007/s12094-020-02360-4. Epub 2020 May 14.
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.
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.
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.
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.
具有最小分化的急性髓细胞性白血病（AML-M0）是一种预后不良的急性白血病亚型。最近的研究表明，长非编码 RNA（lncRNA）在细胞周期控制和增殖等不同细胞过程中发挥着重要作用。浆细胞瘤变异易位 1（PVT1）是那些在 AML 中显著上调的 lncRNA 之一。lncRNA 可以通过锁核酸（LNA）被下调或阻断，LNA 是寡核苷酸链。
在这项研究中，通过反义 LNA GapmeRs 阻断人骨髓癌细胞中的 lncRNA PVT1。在转染后 24、48 和 72 小时，用 PVT1 反义 LNA GapmeRs 转染细胞。通过定量逆转录聚合酶链反应（qRT-PCR）评估 PVT1 和 c-Myc 的表达。通过 MTT 测定评估细胞活力，通过 Annexin V/碘化丙啶染色测定评估细胞凋亡和坏死。
本研究结果表明，在白血病细胞中下调 PVT1 可诱导细胞凋亡、坏死并降低细胞活力。阻断 PVT1 可下调 c-Myc 的表达，表明这两个基因的表达相关。
研究结果表明，抑制 PVT1 可能成为治疗 AML-M0 的新靶点，并有助于寻找副作用更少的治疗方法。
