Acute myeloid leukemia (AML) is a hematologic disease associated with genetic abnormalities. This study aimed to explore the role of leucine-rich repeat-containing protein 1 (LRRC1) in the malignant activities of AML and to reveal the molecular mechanism related to microtubule actin cross-linking factor 1 (MACF1). GEPIA database was used to analyze the expression of LRRC1 in bone marrow tissues of AML patients and the correlation between LRRC1 expression and survival analysis. LRRC1 was knocked down to assess the change of AML cell proliferation, cell cycle and apoptosis using CCK-8 assay and flow cytometry. Besides, the contents of extracellular acidification and oxygen consumption rates were measured to evaluate the glycolysis. Additionally, the interaction between LRRC1 and MACF1 predicted by MEM database and was verified by co-immunoprecipitation (Co-IP) assay. Then, MACF1 was overexpressed to conduct the rescue experiments. Expression of proteins in β-catenin/c-Myc signaling was detected by western blot. Finally, AML xenograft mouse model was established to observe the impacts of LRRC1 silencing on the tumor development. Notably upregulated LRRC1 expression was observed in bone marrow tissues of AML patients and AML cells, and patients with the higher LRRC1 expression displayed the lower overall survival. LRRC1 depletion promoted cell cycle arrest and apoptosis and inhibited the glycolysis. Co-IP confirmed the interaction between LRRC1 and MACF1. MACF1 upregulation relieved the impacts of LRRC1 knockdown on the malignant activities of AML cells. Moreover, LRRC1 silencing inhibited the development of xenograft tumor growth of HL-60 cells in nude mice, suppressed MACF1 expression and inactivated the β-catenin/c-Myc signaling. Collectively, LRRC1 knockdown suppressed proliferation, glycolysis and promoted apoptosis in AML cells by downregulating MACF1 expression to inactivate β-catenin/c-Myc signaling.

急性髓系白血病（AML）是一种与遗传异常相关的血液系统疾病。本研究旨在探讨富含亮氨酸重复序列的蛋白1（LRRC1）在AML恶性活动中的作用，并揭示微管肌动蛋白交联因子1（MACF1）相关的分子机制。利用GEPIA数据库分析AML患者骨髓组织中LRRC1的表达情况以及LRRC1表达与生存分析的相关性。敲低 LRRC1，使用 CCK-8 测定和流式细胞术评估 AML 细胞增殖、细胞周期和凋亡的变化。此外，还通过测量细胞外酸化含量和耗氧率来评价糖酵解情况。此外，LRRC1 和 MACF1 之间的相互作用由 MEM 数据库预测，并通过免疫共沉淀 (Co-IP) 测定进行验证。然后，MACF1被过度表达以进行救援实验。通过蛋白质印迹检测 β-连环蛋白/c-Myc 信号传导中蛋白质的表达。最后，建立AML异种移植小鼠模型，观察LRRC1沉默对肿瘤发展的影响。在AML患者的骨髓组织和AML细胞中观察到LRRC1表达显着上调，并且LRRC1表达较高的患者的总生存期较低。 LRRC1 耗竭促进细胞周期停滞和细胞凋亡并抑制糖酵解。 Co-IP 证实了 LRRC1 和 MACF1 之间的相互作用。 MACF1上调减轻了LRRC1敲低对AML细胞恶性活动的影响。此外，LRRC1沉默可抑制裸鼠HL-60细胞异种移植肿瘤的生长，抑制MACF1表达并灭活β-catenin/c-Myc信号传导。 总的来说，LRRC1 敲低通过下调 MACF1 表达使 β-catenin/c-Myc 信号失活来抑制 AML 细胞的增殖、糖酵解并促进细胞凋亡。