长链非编码 RNA MALAT1 通过海绵吸附 microRNA-146a 调节 CXCR4 表达来调节急性髓系白血病中的细胞迁移、增殖和凋亡。
Long non-coding RNA MALAT1 modulate cell migration, proliferation and apoptosis by sponging microRNA-146a to regulate CXCR4 expression in acute myeloid leukemia.
机构信息
The department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
The department of Cancer, Cancer Hospital of University of Chinese Academy of Sciences, Beijing, People's Republic of China.
出版信息
Hematology. 2021 Dec;26(1):43-52. doi: 10.1080/16078454.2020.1867781.
OBJECTIVES
To investigate the role of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in acute myeloid leukemia (AML) and analyze the potential regulatory network of MALAT1/miR-146a/ CXCR4.
METHODS
The expressions of MALAT1, miR-146a and CXCR4 were performed by qRT-PCR and Western Blot. We conducted trans-well assay, CCK-8 assay and flow cytometry to evaluate the migration, proliferation and apoptosis of AML cells. Also by using luciferase reporter assay, we investigated the interaction between miR-146a and MALAT1 or CXCR4.
RESULTS
Firstly, MALAT1 and CXCR4 were upregulated while miR-146a was downregulated in AML patients compared with healthy controls. We observed a negative correlation between miR-146a and MALAT1 or CXCR4, but a positive correlation between MALAT1 and CXCR4 in AML patients. MALAT1 knockdown inhibited migration and proliferation but induced apoptosis of HL-60 cells. MALAT1 restrained miR-146a expression by acting as a ceRNA. miR-146a regulated HL-60 cells migration, proliferation and apoptosis by directly targeting CXCR4 expression. Finally, we found that CXCR4 expression was downregulated by MALAT1 knockdown and partially restored by miR-146a abrogation.
CONCLUSIONS
Our results showed that MALAT1 regulates migration, proliferation and apoptosis by sponging miR-146a to regulate CXCR4 expression in AML cells, providing novel insights into the role of MALAT1 as a therapeutic target in AML.
目的
探讨转移相关肺腺癌转录本 1（MALAT1）在急性髓系白血病（AML）中的作用，并分析 MALAT1/miR-146a/CXCR4 的潜在调控网络。
方法
采用 qRT-PCR 和 Western blot 检测 MALAT1、miR-146a 和 CXCR4 的表达。通过 Transwell assay、CCK-8 assay 和流式细胞术评估 AML 细胞的迁移、增殖和凋亡。通过荧光素酶报告基因实验，研究 miR-146a 与 MALAT1 或 CXCR4 的相互作用。
结果
首先，与健康对照组相比，AML 患者中 MALAT1 和 CXCR4 上调，而 miR-146a 下调。我们观察到在 AML 患者中，miR-146a 与 MALAT1 或 CXCR4 呈负相关，而 MALAT1 与 CXCR4 呈正相关。MALAT1 敲低抑制 HL-60 细胞的迁移和增殖，但诱导其凋亡。MALAT1 通过作为 ceRNA 抑制 miR-146a 的表达。miR-146a 通过直接靶向 CXCR4 表达来调节 HL-60 细胞的迁移、增殖和凋亡。最后，我们发现 MALAT1 敲低下调 CXCR4 表达，而 miR-146a 缺失部分恢复了 CXCR4 表达。
结论
我们的研究结果表明，MALAT1 通过海绵吸附 miR-146a 来调节 CXCR4 表达，从而调控 AML 细胞的迁移、增殖和凋亡，为 MALAT1 作为 AML 治疗靶点提供了新的见解。
Zotero 插件