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长链非编码RNA MALAT-1的上调预示急性单核细胞白血病预后不良,并影响其细胞增殖和凋亡。

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

作者信息

Huang Jin-Long, Liu Wei, Tian Li-Hong, Chai Ting-Ting, Liu Yang, Zhang Feng, Fu Hai-Ying, Zhou Hua-Rong, Shen Jian-Zhen

机构信息

Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.

出版信息

Oncol Rep. 2017 Sep;38(3):1353-1362. doi: 10.3892/or.2017.5802. Epub 2017 Jul 10.

Abstract

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.

摘要

转移相关的肺腺癌转录本1(MALAT-1)是一种长链非编码RNA,已被证明是几种癌症中的一种新的预后标志物和基因调节因子,但其在急性髓系白血病(AML)中的潜在作用仍不清楚。本研究调查了MALAT-1在AML中的表达及功能作用。通过实时定量PCR评估MALAT-1的表达。在慢病毒介导的MALAT-1敲低后,通过CCK-8和集落形成试验测定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,与健康对照相比,急性单核细胞白血病(M5)患者中MALAT-1的表达显著增加,与低MALAT-1表达患者的总生存期相比,高MALAT-1表达的M5患者的总生存期明显缩短。细胞实验分析表明,MALAT-1沉默降低了M5细胞(U-937和THP-1)的增殖,抑制了细胞周期进程并增加了凋亡。综上所述,这些发现表明,高MALAT-1表达与M5患者的不良预后密切相关,可能在白血病细胞增殖和凋亡中起作用,并且可能作为一种有前景的诊疗标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eacb/5549035/57e3e7f78cb3/OR-38-03-1353-g00.jpg

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