环状 RNA-PTK2 通过靶向 miR-330-5p/FOXM1 轴促进急性髓系白血病细胞的增殖并抑制其凋亡。
Circ-PTK2 promotes the proliferation and suppressed the apoptosis of acute myeloid leukemia cells through targeting miR-330-5p/FOXM1 axis.
机构信息
Department of Hematology, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China.
Department of Nephrology, Zhuzhou No. 2 Hospital, Zhuzhou, China.
出版信息
Blood Cells Mol Dis. 2021 Feb;86:102506. doi: 10.1016/j.bcmd.2020.102506. Epub 2020 Sep 19.
BACKGROUND
Acute myeloid leukemia (AML) is characterized by malignant clonal disorder of blood cells with high relapse rate and low survival rate. Circular RNAs (circRNAs) have shown their important regulatory roles in AML progression. Here, we intended to disclose the role of circular RNA protein tyrosine kinase 2 (circ-PTK2) in the progression of AML and illustrate the potential working mechanisms.
METHODS
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were conducted to analyze cell proliferation ability, and the apoptosis rate was assessed by flow cytometry. Dual-luciferase reporter assay was used to validate the direct interaction between microRNA-330-5p (miR-330-5p) and circ-PTK2 or forkhead box M1 (FOXM1).
RESULTS
Circ-PTK2 was highly expressed in AML. Circ-PTK2 interference suppressed the proliferation and triggered the apoptosis of AML cells. Circ-PTK2 directly bound to miR-330-5p. Si-circ-PTK2-mediated inhibition on the malignant behaviors of AML cells was partly counteracted by the addition of anti-miR-330-5p. MiR-330-5p directly interacted with FOXM1 messenger RNA (mRNA), and FOXM1 overexpression partly reversed miR-330-5p-induced influence in AML cells. Circ-PTK2 up-regulated FOXM1 expression through sponging miR-330-5p in AML cells.
CONCLUSION
Circ-PTK2 promoted the proliferation and hampered the apoptosis of AML cells through targeting miR-330-5p/FOXM1 axis.
背景
急性髓系白血病（AML）的特征是血细胞恶性克隆紊乱，复发率高，生存率低。环状 RNA（circRNA）在 AML 进展中表现出重要的调节作用。在这里，我们旨在揭示环状 RNA 蛋白酪氨酸激酶 2（circ-PTK2）在 AML 进展中的作用，并阐明其潜在的工作机制。
方法
通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测和集落形成实验分析细胞增殖能力，通过流式细胞术检测细胞凋亡率。双荧光素酶报告实验用于验证 microRNA-330-5p（miR-330-5p）与 circ-PTK2 或叉头框蛋白 M1（FOXM1）之间的直接相互作用。
结果
circ-PTK2 在 AML 中高表达。circ-PTK2 干扰抑制了 AML 细胞的增殖并触发了其凋亡。circ-PTK2 可直接与 miR-330-5p 结合。添加抗 miR-330-5p 部分抵消了 Si-circ-PTK2 对 AML 细胞恶性行为的抑制作用。miR-330-5p 可直接与 FOXM1 信使 RNA（mRNA）相互作用，FOXM1 过表达部分逆转了 miR-330-5p 对 AML 细胞的影响。circ-PTK2 通过在 AML 细胞中海绵吸附 miR-330-5p 来上调 FOXM1 的表达。
结论
circ-PTK2 通过靶向 miR-330-5p/FOXM1 轴促进 AML 细胞的增殖并抑制其凋亡。
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