Background LncRNA NEAT1 has been identified as a tumour driver in many human cancers. However, the underlying mechanism of lncRNA NEAT1 in diffuse large B-cell lymphoma (DLBCL) progression is unclear. Methods The expression levels of NEAT1, GLI1 and miR-34b-5p were detected by RT-qPCR and Western blotting in DLBCL tissues and cell lines. MTT and colony formation assays were performed to examine cell proliferation, while annexin-V staining and TUNEL assays were performed to measure cell apoptosis. The effect of NEAT1, GLI1 and miR-34b-5p on cell cycle-associated proteins was evaluated by Western blotting. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed to investigate the interaction between NEAT1 and miR-34b-5p or GLI1 and miR-34b-5p. Moreover, chromatin immunoprecipitation (ChIP) was performed to demonstrate the interaction between MYC and NEAT1. Results NEAT1 and GLI1 were upregulated while miR-34b-5p was downregulated in DLBCL tissues and cell lines compared to normal controls. Knockdown of NEAT1 or overexpression of miR-34b-5p inhibited cell proliferation but promoted cell apoptosis. Overexpression of NEAT1 reversed GLI1-knockdown induced attenuation of cell proliferation. In other words, NEAT1 acted as a competing endogenous RNA (ceRNA), regulating the miR-34b-5p-GLI1 axis, further affecting the proliferation of DLBCL. Moreover, MYC modulated NEAT1 transcription by directly binding to the NEAT1 promoter. Conclusion We revealed that MYC-regulated NEAT1 promoted DLBCL proliferation via the miR-34b-5p-GLI1 pathway, which could provide a novel therapeutic target for DLBCL.

中文翻译：

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MYC 调节的 lncRNA NEAT1 在弥漫性大 B 细胞淋巴瘤中通过 miR-34b-5p-GLI1 通路促进 B 细胞增殖和淋巴瘤形成。

背景 LncRNA NEAT1 已被确定为许多人类癌症的肿瘤驱动因子。然而，lncRNA NEAT1 在弥漫性大 B 细胞淋巴瘤 (DLBCL) 进展中的潜在机制尚不清楚。方法采用RT-qPCR和Western blotting检测DLBCL组织和细胞系中NEAT1、GLI1和miR-34b-5p的表达水平。进行 MTT 和集落形成测定以检查细胞增殖，而进行膜联蛋白-V 染色和 TUNEL 测定以测量细胞凋亡。通过蛋白质印迹评估 NEAT1、GLI1 和 miR-34b-5p 对细胞周期相关蛋白的影响。采用双荧光素酶报告基因和 RNA 免疫沉淀 (RIP) 测定来研究 NEAT1 和 miR-34b-5p 或 GLI1 和 miR-34b-5p 之间的相互作用。而且，进行染色质免疫沉淀 (ChIP) 以证明 MYC 和 NEAT1 之间的相互作用。结果与正常对照相比，DLBCL 组织和细胞系中 NEAT1 和 GLI1 上调，而 miR-34b-5p 下调。敲除 NEAT1 或过表达 miR-34b-5p 可抑制细胞增殖但促进细胞凋亡。NEAT1 的过表达逆转了 GLI1 敲低诱导的细胞增殖衰减。换言之，NEAT1 作为竞争性内源性 RNA (ceRNA)，调节 miR-34b-5p-GLI1 轴，进一步影响 DLBCL 的增殖。此外，MYC 通过直接与 NEAT1 启动子结合来调节 NEAT1 的转录。结论 我们发现 MYC 调节的 NEAT1 通过 miR-34b-5p-GLI1 通路促进 DLBCL 增殖，这可能为 DLBCL 提供新的治疗靶点。