Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China; School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou 215500, PR China.
Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China; Graduate Department, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China.
Drug Resist Updat. 2024 Sep;76:101120. doi: 10.1016/j.drup.2024.101120. Epub 2024 Jul 22.
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.
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控机制，特别是其与多嘧啶 tract 结合蛋白 1（PTBP1）的相互作用及其对癌症进展和耐药性的影响。
分析 AML 组织和细胞系中 BCL7A 的表达水平，重点关注与启动子过度甲基化的关联。在体外和体内研究了 BCL7A 与 PTBP1 的相互作用以及差异表达的影响。研究了对细胞增殖、周期进展、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）的调控作用。
BCL7A 因启动子过度甲基化而在 AML 中下调，并受 PTBP1 负调控。BCL7A 的上调抑制了 AML 细胞的生长，诱导了细胞凋亡，促进了细胞分化，并减少了细胞向淋巴结的浸润，增强了小鼠模型中的存活率。BCL7A 的过表达上调了 IRF7 并下调了 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 中作为肿瘤抑制因子发挥作用，通过 IRF7/HMGCS1 途径抑制恶性进展并增强药物敏感性。这些发现为改善 AML 治疗结果提供了潜在的治疗靶点。
