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环状RNA RAD18通过调控miR-206/蛋白激酶A催化亚基β（PRKACB）轴促进急性髓系白血病进展。

CircRAD18 Accelerates the Progression of Acute Myeloid Leukemia by Modulation of miR-206/PRKACB Axis.

作者信息

Wang Yanyan, Guo Te, Liu Quan, Xie Xianfei

机构信息

Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

German Cancer Research Center, Heidelberg 69120, Germany.

出版信息

Cancer Manag Res. 2020 Oct 30;12:10887-10896. doi: 10.2147/CMAR.S277432. eCollection 2020.

DOI:10.2147/CMAR.S277432
PMID:33154668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7608482/
Abstract

BACKGROUND

Circular RNAs (circRNAs) play a crucial role in tumorigenesis. However, the effects of circRNAs on acute myeloid leukemia (AML) remain largely unexplored. We explored the function of circRAD18 in AML development.

METHODS

QRT-PCR was performed for the levels of circRAD18, RAD18, microRNA-206 (miR-206) and (). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized for cell proliferation. Flow cytometry analysis was carried out to analyze cell apoptosis and cell cycle process. Transwell assay was manipulated for cell migration and invasion. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay was adopted to verify the interaction between miR-206 and circRAD18 or .

RESULTS

CircRAD18 level was increased in AML patients' blood specimens and AML cell lines compared to normal controls. CircRAD18 knockdown impeded the proliferation, migration and invasion and facilitated the apoptosis and cell cycle arrest in AML cells. Moreover, circRAD18 was identified as a sponge for miR-206, and circRAD18 knockdown-mediated effect on AML cell progression was reversed by miR-206 suppression. Additionally, was the target gene of miR-206. MiR-206 overexpression suppressed the malignant behaviors of AML cells, while elevation restored the effects.

CONCLUSION

CircRAD18 aggravated the malignancy of AML cells through reducing miR-206 expression and elevating expression, indicating circRAD18 might be a therapeutic target for AML.

摘要

背景

环状RNA（circRNAs）在肿瘤发生中起关键作用。然而，circRNAs对急性髓系白血病（AML）的影响在很大程度上仍未得到探索。我们探究了circRAD18在AML发展中的作用。

方法

对circRAD18、RAD18、微小RNA-206（miR-206）和（此处原文缺失信息）的水平进行定量逆转录聚合酶链反应（QRT-PCR）。使用细胞计数试剂盒-8（CCK-8）检测和集落形成试验检测细胞增殖。进行流式细胞术分析以分析细胞凋亡和细胞周期进程。采用Transwell试验检测细胞迁移和侵袭。进行蛋白质印迹试验检测蛋白质水平。采用双荧光素酶报告基因试验验证miR-206与circRAD18或（此处原文缺失信息）之间的相互作用。

结果

与正常对照相比，AML患者血液标本和AML细胞系中circRAD18水平升高。敲低circRAD18可抑制AML细胞的增殖、迁移和侵袭，并促进其凋亡和细胞周期阻滞。此外，circRAD18被鉴定为miR-206的海绵，抑制miR-206可逆转敲低circRAD18介导的对AML细胞进程的影响。另外，（此处原文缺失信息）是miR-206的靶基因。miR-206过表达抑制AML细胞的恶性行为，而（此处原文缺失信息）升高可恢复这些作用。

结论

circRAD18通过降低miR-206表达和升高（此处原文缺失信息）表达加重AML细胞的恶性程度，表明circRAD18可能是AML的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/b85d731cff80/CMAR-12-10887-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/209733ae3b65/CMAR-12-10887-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/adbe2cd8608c/CMAR-12-10887-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/3f14a395806f/CMAR-12-10887-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/1e38a9530621/CMAR-12-10887-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/bfd076472099/CMAR-12-10887-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/b85d731cff80/CMAR-12-10887-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/209733ae3b65/CMAR-12-10887-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/adbe2cd8608c/CMAR-12-10887-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/3f14a395806f/CMAR-12-10887-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/1e38a9530621/CMAR-12-10887-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/bfd076472099/CMAR-12-10887-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ca/7608482/b85d731cff80/CMAR-12-10887-g0006.jpg

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