Li Xiaoyan, Qian Qiyi, Li Juejiashan, Zhang Lu, Wang Lifang, Huang Dongsheng, Xu Qiuran, Chen Wenhu
School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, China.
School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Cell Death Dis. 2025 Aug 8;16(1):599. doi: 10.1038/s41419-025-07926-0.
Acute myeloid leukemia (AML) is a blood cancer characterized by uncontrolled growth of myeloid cells. Overcoming AML treatment resistance, particularly to anthracycline-based drugs like doxorubicin (ADR), poses a challenge. This study investigated the role of CELF1, an RNA-binding protein, in ADR resistance and autophagy regulation in AML. CELF1 expression was elevated in multiple tumor types, including AML. AML cell lines exhibit varying levels of CELF1 expression, with drug-resistant cell lines showing higher CELF1 expression compared to parental cells. CELF1 knockdown reduced drug resistance, promoted cell death, and inhibited autophagy. Mechanistic analysis identified ATG5 as a potential CELF1-regulated target gene, with CELF1 knockdown reducing ATG5 expression and mRNA decay. These findings indicate that targeting CELF1 could overcome ADR resistance in AML by modulating autophagy through ATG5 regulation, highlighting its clinical significance as a therapeutic target for enhancing ADR response in AML.
急性髓系白血病（AML）是一种以髓系细胞不受控制地生长为特征的血癌。克服AML治疗耐药性，尤其是对多柔比星（ADR）等基于蒽环类药物的耐药性，是一项挑战。本研究调查了RNA结合蛋白CELF1在AML中对ADR耐药性和自噬调节的作用。CELF1在包括AML在内的多种肿瘤类型中表达升高。AML细胞系表现出不同水平的CELF1表达，与亲本细胞相比，耐药细胞系显示出更高的CELF1表达。CELF1敲低降低了耐药性，促进了细胞死亡，并抑制了自噬。机制分析确定ATG5是一个潜在的CELF1调节靶基因，CELF1敲低降低了ATG5表达和mRNA降解。这些发现表明，靶向CELF1可通过调节ATG5来调控自噬，从而克服AML中的ADR耐药性，突出了其作为增强AML中ADR反应的治疗靶点的临床意义。
