Yao Lei, Zhang Xinyang, Li Xiaoqing, Xu Jin, Yang Siqi, Li Fengyue, Chen Wenbo, Shan Yuxin, Ren Linli, Zhuo Chenjian, Liang Sisi, Chen Lu, Yin Weinan, Liu Hudan, Liu Lingbo, Feng Mingqian, Chen Ke, Chen Shuliang, He Chunjiang
College of Biomedicine and Health, Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
TaiKang Medical School, Wuhan University, Wuhan, China.
Oncogene. 2025 May;44(18):1234-1244. doi: 10.1038/s41388-025-03299-y. Epub 2025 Feb 10.
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.
急性髓系白血病（AML）是一种由多种分子机制引起的复杂疾病。作为一种重要的调节分子，环状RNA（circRNA）在AML中的作用尚未完全明确。通过对临床样本进行高通量测序，我们系统地鉴定了AML样本与健康供体样本之间circRNA表达和分布的差异。发现一种环状RNA，即circAFF2，在AML患者中显著上调。功能研究表明，敲低circAFF2可显著抑制AML细胞的增殖并促进其凋亡。circAFF2的过表达则会产生相反的效果。体内实验表明，与对照组相比，移植敲低circAFF2的AML细胞可减缓小鼠的增殖和浸润，并延长其生存时间。进一步研究表明，circAFF2可通过与早幼粒细胞白血病（PML）mRNA的3'非翻译区（3'UTR）结合来促进PML mRNA的降解，从而影响AML细胞的增殖和凋亡。总之，我们的研究表明circAFF2可与PML mRNA结合以调节AML细胞功能，为AML的发病机制提供了新见解，并为临床诊断和治疗提供了潜在靶点。
