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长链非编码 RNA 牛磺酸上调基因 1 与疾病状况和预后的相关性,及其对急性髓系白血病细胞活性的影响。

Correlation of long non-coding RNA taurine-upregulated gene 1 with disease conditions and prognosis, as well as its effect on cell activities in acute myeloid leukemia.

出版信息

Cancer Biomark. 2018;23(4):569-577. doi: 10.3233/CBM-181834.

DOI:10.3233/CBM-181834
PMID:30452403
Abstract

OBJECTIVE

This study aimed to investigate the correlation of long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) with clinicopathological characteristics and prognosis in acute myeloid leukemia (AML) patients, as well as its function in cell proliferation and apoptosis.

METHODS

Two hundred and thirty six de novo AML patients were consecutively enrolled and then underwent conventional induction chemotherapy. Bone marrow samples were obtained from all AML patients and controls. Quantitative polymerase chain reaction assay was performed to detect lncRNA TUG1 expression. KG-1 cells were transfected by TUG1 inhibitor (TUG1 (-)) and blank inhibitor (NC (-)) plasmids. Cell proliferation and apoptosis were evaluated by CCK8 and AV/PI assays, and apoptotic markers expressions were detected by Western blot assay.

RESULTS

LncRNA TUG1 expression was higher in AML patients compared to controls, and it was positively correlated with white blood cell counts as well as poor risk stratification. Additionally, elevated lncRNA TUG1 expression was observed in non-complete remission (non-CR) patients compared to CR patients, and it was correlated with shorter event-free survival and overall survival in AML patients. In the in vitro experiments, lncRNA TUG1 expression was upregulated in AML cell lines compared to control cells, and cell proliferation ability was reduced, but cell apoptosis rate was promoted in TUG1 (-) group compared to NC (-) group at 72 hours after transfection in KG-1 cells.

CONCLUSIONS

LncRNA TUG1 predicts advanced disease conditions and poor prognosis in AML patients, and its knockout decreases proliferation and increases apoptosis of AML cells.

摘要

目的

本研究旨在探讨长链非编码 RNA 牛磺酸上调基因 1(lncRNA TUG1)与急性髓系白血病(AML)患者临床病理特征和预后的相关性及其在细胞增殖和凋亡中的作用。

方法

连续纳入 236 例初诊 AML 患者,并进行常规诱导化疗。所有 AML 患者和对照者均采集骨髓样本。采用实时定量聚合酶链反应检测 lncRNA TUG1 表达。采用 TUG1 抑制剂(TUG1(-))和空白抑制剂(NC(-))质粒转染 KG-1 细胞。采用 CCK8 和 AV/PI 检测细胞增殖和凋亡,Western blot 检测凋亡标志物表达。

结果

与对照组相比,AML 患者的 lncRNA TUG1 表达水平升高,且与白细胞计数升高以及风险分层不良呈正相关。此外,与完全缓解(CR)患者相比,未缓解(non-CR)患者中 lncRNA TUG1 表达升高,且与 AML 患者的无事件生存和总生存时间缩短相关。在体外实验中,与对照组相比,AML 细胞系中的 lncRNA TUG1 表达上调,且在转染 72 小时后,TUG1(-)组的细胞增殖能力降低,但细胞凋亡率高于 NC(-)组。

结论

lncRNA TUG1 预测 AML 患者病情进展和预后不良,其敲除可降低 AML 细胞的增殖能力并促进其凋亡。

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