This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance. BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with promoter hypermethylation. Interaction with PTBP1 and effects of differential expression of BCL7A were examined in vitro and in vivo. The impacts on cell proliferation, cycle progression, apoptosis, and differentiation were studied. Additionally, the regulatory roles of BCL7A on interferon regulatory factor 7 (IRF7) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were assessed. BCL7A was downregulated in AML due to promoter hypermethylation and negatively regulated by PTBP1. Upregulation of BCL7A impeded AML cell growth, induced apoptosis, promoted cell differentiation, and decreased cell infiltration into lymph nodes, enhancing survival in mouse models. Overexpression of BCL7A upregulated IRF7 and downregulated HMGCS1, linking to reduced AML cell malignancy and decreased resistance to cytarabine. BCL7A acts as a tumor suppressor in AML, inhibiting malignant progression and enhancing drug sensitivity through the IRF7/HMGCS1 pathway. These findings suggest potential therapeutic targets for improving AML treatment outcomes.

中文翻译：

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BCL7A 抑制急性髓系白血病的进展和耐药性


本研究旨在阐明 B 细胞淋巴瘤 7 蛋白家族成员 A (BCL7A) 在急性髓系白血病 (AML) 中的生物学作用和调节机制，特别是其与多嘧啶束结合蛋白 1 (PTBP1) 的相互作用以及对癌症进展的影响和耐药性。对 AML 组织和细胞系中的 BCL7A 表达水平进行了分析，重点关注与启动子高甲基化的关联。在体外和体内检查了与 PTBP1 的相互作用以及 BCL7A 差异表达的影响。研究了对细胞增殖、周期进程、细胞凋亡和分化的影响。此外，还评估了 BCL7A 对干扰素调节因子 7 (IRF7) 和 3-羟基-3-甲基戊二酰辅酶 A 合酶 1 (HMGCS1) 的调节作用。 BCL7A 在 AML 中由于启动子高甲基化而下调，并受到 PTBP1 的负向调节。 BCL7A 的上调可阻碍 AML 细胞生长、诱导细胞凋亡、促进细胞分化并减少细胞浸润到淋巴结，从而提高小鼠模型的存活率。 BCL7A 的过度表达上调 IRF7 并下调 HMGCS1，与 AML 细胞恶性程度降低和阿糖胞苷耐药性降低有关。 BCL7A 在 AML 中充当肿瘤抑制因子，通过 IRF7/HMGCS1 途径抑制恶性进展并增强药物敏感性。这些发现提出了改善 AML 治疗结果的潜在治疗靶点。