circAFF2 promotes the development of AML by binding to PML mRNA

IF 7.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Oncogene Pub Date : 2025-02-10 DOI:10.1038/s41388-025-03299-y
Lei Yao, Xinyang Zhang, Xiaoqing Li, Jin Xu, Siqi Yang, Fengyue Li, Wenbo Chen, Yuxin Shan, Linli Ren, Chenjian Zhuo, Sisi Liang, Lu Chen, Weinan Yin, Hudan Liu, Lingbo Liu, Mingqian Feng, Ke Chen, Shuliang Chen, Chunjiang He
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Abstract

AML is a complex disease caused by multiple molecular mechanisms. As an important regulatory molecule, the role of circRNA in AML is not fully understood. By performing high-throughput sequencing on clinical samples, we systematically identified the differences in circRNA expression and distribution between AML and healthy donor samples. One circular RNA, circAFF2, was found to be significantly upregulated in AML patients. Functional studies showed that knockdown of circAFF2 could significantly inhibit the proliferation of AML cells and promote their apoptosis. Overexpression of circAFF2 can have opposite effects. In vivo experiments showed that transplantation of AML cells with circAFF2 knockdown slowed the proliferation and infiltration and prolonged the survival time of mice compared to controls. Further studies showed that circAFF2 can promote the degradation of PML mRNA by binding to the 3’UTR of PML mRNA, thereby affecting the proliferation and apoptosis of AML cells. In conclusion, our work demonstrates that circAFF2 can bind to PML mRNA to regulate AML cell function, providing new insights into the mechanism of AML development and potential targets for clinical diagnosis and treatment.

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circAFF2通过结合PML mRNA促进AML的发展。
AML是一种由多种分子机制引起的复杂疾病。作为一种重要的调控分子,circRNA在AML中的作用尚不完全清楚。通过对临床样本进行高通量测序,我们系统地鉴定了AML和健康供体样本之间circRNA表达和分布的差异。一种环状RNA circAFF2在AML患者中被发现显著上调。功能研究表明,敲低circAFF2可显著抑制AML细胞增殖,促进其凋亡。过表达circAFF2会产生相反的效果。体内实验表明,与对照组相比,circAFF2敲低的AML细胞移植可减缓小鼠的增殖和浸润,延长小鼠的存活时间。进一步研究表明,circAFF2可以通过结合PML mRNA的3'UTR促进PML mRNA的降解,从而影响AML细胞的增殖和凋亡。总之,我们的工作表明circAFF2可以结合PML mRNA调节AML细胞功能,为AML的发展机制和临床诊断和治疗的潜在靶点提供了新的见解。
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来源期刊
Oncogene
Oncogene 医学-生化与分子生物学
CiteScore
15.30
自引率
1.20%
发文量
404
审稿时长
1 months
期刊介绍: Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.
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