Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
Int J Biochem Cell Biol. 2018 May;98:54-64. doi: 10.1016/j.biocel.2018.03.001. Epub 2018 Mar 21.
Cancerous cells show resistance to various forms of therapy, so applying up to the minute targeted therapy is crucial. For this purpose, long non-coding RNA PVT1 as shown by recent studies is an important oncogene that interacts with vital cellular signaling pathways and different proteins such as c-Myc, NOP2 and LATS2. Due to the enormous role of long non-coding RNAs in development of leukemias, we aimed to show the role of PVT1 knock-down on fate of different hematologic cell lines. owing to this matter, various experiments such as Real-time PCR, cell cycle analysis and apoptosis assay were performed. Meanwhile, proliferation rate by CFSE, protein expression of c-Myc and hTERT by western blot and flow cytometry analysis were investigated. Our results demonstrated that PVT1 knock-down results in c-Myc degradation, proliferation down-regulation, induction of apoptosis and G0/G1 arrest. Simultaneously, for the first time, we posited the relation between this oncogene with hTERT that reduced after PVT1 knock-down. Considering these results, long non-coding RNA PVT1 may be a potential option for targeted therapy in hematologic malignancies.
癌细胞对各种形式的治疗有耐药性,因此应用最新的靶向治疗至关重要。为此,最近的研究表明,长链非编码 RNA PVT1 是一种重要的癌基因,它与重要的细胞信号通路和不同的蛋白质(如 c-Myc、NOP2 和 LATS2)相互作用。由于长链非编码 RNA 在白血病的发展中起着巨大的作用,我们旨在展示 PVT1 敲低对不同血液细胞系命运的影响。为此,进行了各种实验,如实时 PCR、细胞周期分析和凋亡测定。同时,通过 CFSE 研究增殖率,通过 Western blot 和流式细胞术分析检测 c-Myc 和 hTERT 的蛋白表达。我们的结果表明,PVT1 敲低导致 c-Myc 降解、增殖下调、诱导凋亡和 G0/G1 期阻滞。同时,我们首次提出了这个癌基因与 hTERT 之间的关系,PVT1 敲低后 hTERT 减少。考虑到这些结果,长链非编码 RNA PVT1 可能是血液恶性肿瘤靶向治疗的一个潜在选择。