Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis

Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis
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DOI:
10.3349/ymj.2020.61.1.20
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发表时间:
2020-01-01
影响因子:
2.4
通讯作者:
Yao, Rui
Yao, Rui
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Ling;Zhan, Cheng-Zhi;Yao, Rui

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目的:姜黄素在人类肿瘤中发挥其抗癌作用,部分是通过靶向特定的microRNA。miR-21是多种人类癌症的致癌作用的关键。本研究旨在进一步探讨姜黄素和miR-21在弥漫性大B细胞淋巴瘤(DLBCL)中的作用机制。材料和方法:采用实时荧光定量PCR方法检测mill-21和VHL mRNA的表达水平。采用原位杂交法观察淋巴瘤组织中miR-21的表达。Westernblot检测VHL蛋白、Ki-67、caspase-3和deaved caspase-3的表达。采用双荧光素酶报告基因分析和RNA免疫沉淀分析确定miR-21的直接靶点。结果:姜黄素可抑制SU-DIIL-8细胞的增殖、迁移和侵袭能力,促进细胞凋亡。姜黄素抑制miR-21的表达,姜黄素通过miR-21在SU-DHL-8细胞中发挥其抗增殖、抗迁移、抗侵袭和促凋亡作用。VHL是miR-21的直接靶点。结论:姜黄素可能通过抑制miR-21发挥其抗增殖、抗迁移、抗侵袭和促凋亡作用。并调节DLBBCL细胞系中VHL的表达。我们的研究结果提供了一个可能的分子机制,姜黄素介导的抗癌作用。
Purpose: Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key on-comir in carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link between curcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL).Materials and Methods: Quantitative real-time PCR assays were performed to assess the levels of mill-21 and Von Hippel-Lindau (VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was used for determination of VHL protein, Ki-67, caspase-3, and deaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assay were used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively.Results: Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DIIL-8 cells. Curcumin inhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SU-HL-8 cells by VHL.Conclusion: Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, by repressing miR-21. and regulating VHL expression in DLBBCL cell line. Our findings provided a possible molecular mechanism of curcumin-mediated anti-cancer effect.