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Upregulation of long non-coding RNA MALAT-1 confers poor prognosis and influences cell proliferation and apoptosis in acute monocytic leukemia

机译:长期非编码RNA MALAT-1的上调赋予不良预后并影响急性单核细胞白血病的细胞增殖和凋亡

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摘要

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long non-coding RNA, has been documented to be a new prognostic marker and gene regulator in several types of cancer, but its potential involvement in acute myeloid leukemia (AML) remains unclear. This study investigated the expression and functional role of MALAT-1 in AML. MALAT-1 expression was assessed by real-time quantitative PCR. After lentiviral-mediated MALAT-1 knockdown, the proliferation of AML cells was determined by CCK-8 and colony formation assays. Cell cycle progression and apoptosis were evaluated by flow cytometry and the expression of caspase-3, −8 and −9 was assessed by western blot analysis. We found that MALAT-1 expression in patients with acute monocytic leukemia (M5) was significantly increased when compared with that of healthy controls, and the overall survival of M5 patients with high MALAT-1 expression was markedly reduced when compared with the overall survival of patients with low MALAT-1 expression. The analysis of cellular experiments showed that MALAT-1 silencing decreased the proliferation of M5 cells (U-937 and THP-1), inhibited cell cycle progression and increased apoptosis. Taken together, these findings suggest that high MALAT-1 expression is closely associated with poor prognosis in M5 patients and may play a role in leukemia cell proliferation and apoptosis, and may serve as a promising theranostic marker.
机译:转移相关的肺腺癌转录本1(MALAT-1)是一种长的非编码RNA,已被证明是几种类型癌症中的一种新的预后标志物和基因调节剂,但其潜在的参与急性髓细胞性白血病(AML)的能力仍然存在不清楚。本研究调查了MALAT-1在AML中的表达及其功能。通过实时定量PCR评估MALAT-1表达。慢病毒介导的MALAT-1敲低后,通过CCK-8和集落形成试验确定AML细胞的增殖。通过流式细胞术评估细胞周期进程和凋亡,并通过蛋白质印迹分析评估caspase-3,-8和-9的表达。我们发现,与健康对照组相比,急性单核细胞白血病(M5)患者中MALAT-1表达显着增加,而与MALAT-1高表达的M5患者相比,其总生存期显着降低。 MALAT-1表达低的患者。细胞实验分析表明,MALAT-1沉默可降低M5细胞(U-937和THP-1)的增殖,抑制细胞周期进程并增加细胞凋亡。综上所述,这些发现表明,MALAT-1的高表达与M5患者的不良预后密切相关,并且可能在白血病细胞的增殖和凋亡中发挥作用,并且可以作为有希望的治疗学标志物。

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