Department of Hematology, Hainan Province Clinical Medical Center, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China.
School of Preventive Medicine, Hainan Medical University, Haikou, Hainan Province, China.
Int J Lab Hematol. 2024 Oct;46(5):885-893. doi: 10.1111/ijlh.14310. Epub 2024 May 22.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.
Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.
Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b.
FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.
弥漫性大 B 细胞淋巴瘤（DLBCL）是最常见的淋巴瘤类型，导致许多患者失去了宝贵的生命。FOXO3 是多种癌症的抑制剂，但 FOXO3 在 DLBCL 中的作用和机制尚不清楚。
采用生物信息学分析提供 FOXO3 表达及其对 DLBCL 患者预后的信息。使用 RT-qPCR 和 Western blot 评估基因和蛋白质的丰度。通过 CCK-8 和流式细胞术检测细胞增殖和凋亡。通过 TransmiR 和 Starbase 预测 FOXO3、miR-34b 和 HSPG2 之间的相互作用，并通过双荧光素酶报告基因检测、ChIP 检测和 RIP 检测进行验证。
我们的研究结果表明，FOXO3 在 DLBCL 细胞中表达异常下调。FOXO3 的上调抑制了 DLBCL 细胞的增殖并促进了细胞凋亡，而 miR-34b 抑制剂消除了这些影响。同样，miR-34b 模拟物抑制了 DLBCL 细胞的恶性行为，而过表达 HSPG2 则消除了这些影响。机制上，FOXO3 通过与 miR-34b 启动子相互作用诱导 miR-34b 的表达，而 HSPG2 是 miR-34b 的靶向基因。
FOXO3 通过影响 miR-34b/HSPG2 轴减弱了 DLBCL 细胞的增殖能力并促进了细胞凋亡率，从而抑制了 DLBCL 的进展。
