环状 RNA 0001602 通过调控 miR-192-5p/ZBTB20 轴加剧急性髓系白血病的进展。

Circ_0001602 aggravates the progression of acute myeloid leukemia by regulating the miR-192-5p/ZBTB20 axis.

机构信息

Department of Hematology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, People's Republic of China.

出版信息

Hematology. 2023 Dec;28(1):2240133. doi: 10.1080/16078454.2023.2240133.

DOI:10.1080/16078454.2023.2240133

PMID:37585722

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a malignant blood cancer with a poor prognosis and complex pathogenesis. Recently, the critical role of circular RNAs (circRNAs) has been demonstrated in the malignant progression of AML. This study aimed to investigate the functional role and underlying mechanism of circ_0001602 in AML development.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted for detecting the expression of circ_0001602, CCND3, microRNA-192-5p (miR-192-5p), and Zinc Finger and BTB Domain-Containing Protein 20 (ZBTB20) mRNA. RNase R assay and Actinomycin D assay were implemented to determine the characteristics of circ_0001602. Cell counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Flow cytometry was employed for assessing cell cycle distribution and apoptosis. Dual-luciferase reporter assay and RIP assay were utilized for confirming the interactions between miR-192-5p and circ_0001602 or ZBTB20.

RESULTS

Circ_0001602 and ZBTB20 were upregulated and miR-192-5p level was reduced in AML tissues and cells. Depletion of circ_0001602 repressed cell proliferation and induced cell cycle arrest and apoptosis in AML cells. Functionally, circ_0001602 was identified to be the sponge of miR-192-5p, and miR-192-5p silence restored the suppressive effects of circ_0001602 knockdown on AML cell progression. Furthermore, ZBTB20 was a target of miR-192-5p, and ZBTB20 overexpression neutralized the miR-192-5p-mediated inhibiting actions on the malignant phenotypes of AML cells. Besides, circ_0001602 could sponge miR-192-5p to positively regulate ZBTB20 expression.

CONCLUSION

Circ_0001602 contributed to AML cell development at least partially through modulating the miR-192-5p/ZBTB20 axis, which provided new insights for AML treatment.

摘要

背景

急性髓细胞白血病（AML）是一种预后不良且发病机制复杂的恶性血液病。最近，环状 RNA（circRNA）的关键作用已被证明在 AML 的恶性进展中起作用。本研究旨在探讨 circ_0001602 在 AML 发展中的功能作用和潜在机制。

方法

采用实时定量聚合酶链反应（qRT-PCR）检测 circ_0001602、CCND3、微小 RNA-192-5p（miR-192-5p）和锌指和 BTB 结构域包含蛋白 20（ZBTB20）mRNA 的表达。采用 RNase R 试验和放线菌素 D 试验确定 circ_0001602 的特征。采用细胞计数试剂盒-8（CCK-8）试验评估细胞增殖。采用流式细胞术评估细胞周期分布和细胞凋亡。采用双荧光素酶报告基因试验和 RIP 试验证实 miR-192-5p 与 circ_0001602 或 ZBTB20 之间的相互作用。

结果

circ_0001602 和 ZBTB20 在 AML 组织和细胞中上调，而 miR-192-5p 水平降低。circ_0001602 缺失抑制 AML 细胞增殖，并诱导 AML 细胞周期停滞和凋亡。功能上，circ_0001602 被鉴定为 miR-192-5p 的海绵，而 miR-192-5p 沉默恢复了 circ_0001602 敲低对 AML 细胞进展的抑制作用。此外，ZBTB20 是 miR-192-5p 的靶标，ZBTB20 过表达中和了 miR-192-5p 对 AML 细胞恶性表型的抑制作用。此外，circ_0001602 可以海绵 miR-192-5p 来正向调节 ZBTB20 表达。