Liu Wenyuan, Yin Hongli, Xie Zhiwei, Fang Fang, Chu Jinhua, Yang Linhai, Huang Lingling, Tu Songji, Cai Huaju, Wu Zhengyu, Wei Anbang, Liu Chengzhu, Hong Yi, Tian Xiaotong, Cheng Yan, Pan Jian, Wang Ningling, Zhang Kunlong
Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei City, 230601, Anhui Province, China.
Institute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou City, 215003, China.
Mol Cell Biochem. 2025 Feb;480(2):985-999. doi: 10.1007/s11010-024-04992-4. Epub 2024 May 3.
Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.
急性髓系白血病（AML）是一种罕见的异质性疾病。在过去几十年中，随着治疗方法的不断改进，患者预后有所改善，但一些原发性耐药或治疗后复发的患者预后仍然较差。迫切需要额外的治疗方法来改善这些患者的预后。FYB1在AML组织和正常组织中的表达存在显著差异。FYB1高表达与较差的总生存期（OS）相关，这表明FYB1可能调节AML的进展。因此，了解FYB1对AML的影响可以提高治疗方法的成功率和AML患者的预后。在本研究中，通过对大型数据库的分析以及体内和体外实验，我们评估了FYB1在AML中的表达和作用以及FYB与患者预后的关系。通过RNA测序分析了FYB1基因的下游靶点。利用数据库挖掘和体外实验进一步阐明下游靶点凝溶胶蛋白样肌动蛋白封端蛋白（CAPG）对AML细胞的影响及其与患者预后的关系。FYB1在AML组织中的表达显著更高，且与预后不良相关。敲低FYB1可抑制AML细胞增殖，促进细胞凋亡，降低细胞黏附能力，并显著降低小鼠肿瘤形成率。此外，敲低FYB1可导致CAPG表达显著降低。抑制CAPG可显著抑制细胞增殖并增加细胞凋亡。本研究的结论强调了FYB1/CAPG轴在促进AML中的关键作用。我们提出FYB1/CAPG轴可作为AML治疗策略开发的新线索。
