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长链非编码RNA-H19通过靶向微小RNA-29a-3p抑制急性髓系白血病细胞凋亡。

LncRNA-H19 inhibits apoptosis of acute myeloid leukemia cells via targeting miR-29a-3p.

作者信息

Zhao T-T, Liu X

机构信息

Department of Laboratory Medicine, Affiliated Municipal Hospital of Xuzhou Medical University, Xuzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):224-231. doi: 10.26355/eurrev_201908_18651.

DOI:10.26355/eurrev_201908_18651
PMID:31389605
Abstract

OBJECTIVE

To explore the influences of long non-coding ribonucleic acid (lncRNA)-H19 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells via the Wnt signaling pathway.

PATIENTS AND METHODS

Blood samples were collected from 40 AML patients. The AML cells were cultured. Cell counting kit-8 (CCK-8) was used to detect cell proliferation and flow cytometry was applied to analyze cell cycle and determine the apoptosis rate. Moreover, the action target of lncRNA-H19 was detected through a dual-luciferase reporter assay and Western blotting was performed to detect the change in protein level.

RESULTS

The expression of lncRNA-H19 in AML patients was markedly higher than that in normal controls and compared with human embryonic kidney (HEK)-293T cells, AML cell Kasumi-1 exhibited an increased lncRNA-H19 expression. LncRNA-H19 could promote cell proliferation, but suppress cell apoptosis. It is bound to micro RNA (miR)-29a-3p in a targeted manner. and the expression level of miR-29a-3p in AML patients was prominently lower than that in normal controls. After miR-29a-3p was inhibited, the expression of intranuclear β-catenin was significantly increased and the Wnt/β-catenin pathway critical molecules T-cell factor (TCF) and lymphoid enhancer factor 1 (LEF1) were evidently up-regulated after the down-regulation of miR-29a-3p.

CONCLUSIONS

LncRNA-H19 targets miR-29a-3p to promote the proliferation of AML cells, but inhibit the apoptosis through the Wnt/ β-catenin signaling pathway.

摘要

目的

探讨长链非编码核糖核酸(lncRNA)-H19通过Wnt信号通路对急性髓系白血病(AML)细胞增殖和凋亡的影响。

患者与方法

收集40例AML患者的血液样本。培养AML细胞。采用细胞计数试剂盒-8(CCK-8)检测细胞增殖情况,应用流式细胞术分析细胞周期并测定凋亡率。此外,通过双荧光素酶报告基因检测法检测lncRNA-H19的作用靶点,并进行蛋白质免疫印迹法检测蛋白水平变化。

结果

AML患者lncRNA-H19的表达明显高于正常对照组,与人类胚胎肾(HEK)-293T细胞相比,AML细胞Kasumi-1的lncRNA-H19表达增加。LncRNA-H19可促进细胞增殖,但抑制细胞凋亡。它以靶向方式与微小RNA(miR)-29a-3p结合,AML患者中miR-29a-3p的表达水平显著低于正常对照组。抑制miR-29a-3p后,核内β-连环蛋白的表达显著增加,miR-29a-3p下调后,Wnt/β-连环蛋白通路关键分子T细胞因子(TCF)和淋巴细胞增强因子1(LEF1)明显上调。

结论

LncRNA-H19靶向miR-29a-3p,促进AML细胞增殖,但通过Wnt/β-连环蛋白信号通路抑制细胞凋亡。

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