关键词: AML ZBTB20 circ_0001602 miR-192-5p

Mesh : Humans Apoptosis / genetics Cell Count Cell Cycle Cell Proliferation Leukemia, Myeloid, Acute / genetics MicroRNAs / genetics Nerve Tissue Proteins Transcription Factors RNA, Circular / genetics

来  源:   DOI:10.1080/16078454.2023.2240133

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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:
急性髓系白血病(AML)是一种预后不良、发病机制复杂的恶性血癌。最近,环状RNA(circularRNAs,circRNAs)在AML恶性进展中的关键作用已得到证实.本研究旨在探讨circ_0001602在AML发生发展中的作用机制。
进行定量实时聚合酶链反应(qRT-PCR)检测circ_0001602,CCND3,microRNA-192-5p(miR-192-5p)的表达,和锌指和含BTB结构域的蛋白20(ZBTB20)mRNA。实施RNaseR测定和放线菌素D测定以确定circ_0001602的特征。进行细胞计数试剂盒-8(CCK-8)测定以评估细胞增殖。流式细胞术用于评估细胞周期分布和细胞凋亡。双荧光素酶报告基因测定和RIP测定用于确认miR-192-5p与circ_0001602或ZBTB20之间的相互作用。
Circ_0001602和ZBTB20上调,miR-192-5p水平在AML组织和细胞中降低。circ_0001602的耗尽抑制AML细胞的细胞增殖并诱导细胞周期停滞和凋亡。功能上,circ_0001602被鉴定为miR-192-5p的海绵,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,和ZBTB20过表达中和miR-192-5p介导的对AML细胞恶性表型的抑制作用。此外,circ_0001602可以海绵化miR-192-5p正向调节ZBTB20的表达。
Circ_0001602至少部分通过调节miR-192-5p/ZBTB20轴促进AML细胞发育,这为AML治疗提供了新的见解。
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