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MicroRNA-429 inhibits neuroblastoma cell proliferation, migration and invasion via the NF-κB pathway.
Cellular & Molecular Biology Letters ( IF 9.2 ) Pub Date : 2020-02-13 , DOI: 10.1186/s11658-020-0202-9
Xianjun Zhou 1 , Hongting Lu 1 , Fujiang Li 1 , Xiwei Hao 1 , Lulu Han 2 , Qian Dong 1 , Xin Chen 1
Affiliation  

MicroRNAs (miRNAs or miRs) can participate in the development and progression of neuroblastoma. Many studies have indicated that miR-429 can participate in tumor development. However, the mechanism underlying miR-429-mediated progression of neuroblastoma remains largely unclear. Colony formation and apoptosis assays were used to determine the effect of miR-429 on cell proliferation. Its impact on cell migration was determined using the wound-healing and Transwell assays. The target gene of miR-429 was confirmed via western blotting and luciferase reporter assays. A nude mouse xenograft model with miR-429 overexpression was used to assess the effect on tumor growth. Our findings indicate that miR-429 is downregulated in neuroblastoma cell lines. We also found that it can induce apoptosis and inhibit proliferation in cells of those lines. MiR-429 can bind to the 3′-UTR of IKKβ mRNA and overexpression of IKKβ can reverse cell proliferation, blocking the effect of miR-429. Furthermore, miR-429 overexpression inhibited neuroblastoma growth in our nude mouse xenograft model. We provide important insight into miR-429 as a tumor suppressor through interaction with IKKβ, which is a catalytic subunit of the IKK complex that activates NF-κB nuclear transport. Our results demonstrate that miR-429 may be a new target for the treatment of neuroblastoma.

中文翻译:

MicroRNA-429 通过 NF-κB 通路抑制神经母细胞瘤细胞的增殖、迁移和侵袭。

MicroRNAs(miRNAs或miRs)可以参与神经母细胞瘤的发展和进展。许多研究表明miR-429可以参与肿瘤的发展。然而,miR-429介导的神经母细胞瘤进展的机制仍不清楚。集落形成和细胞凋亡测定用于确定miR-429对细胞增殖的影响。使用伤口愈合和 Transwell 测定法确定其对细胞迁移的影响。miR-429 的靶基因通过蛋白质印迹和荧光素酶报告基因测定得到证实。使用具有 miR-429 过表达的裸鼠异种移植模型来评估对肿瘤生长的影响。我们的研究结果表明 miR-429 在神经母细胞瘤细胞系中下调。我们还发现它可以诱导细胞凋亡并抑制这些细胞系的细胞增殖。MiR-429 可以与 IKKβ mRNA 的 3'-UTR 结合,IKKβ 的过表达可以逆转细胞增殖,阻断 miR-429 的作用。此外,在我们的裸鼠异种移植模型中,miR-429 过表达抑制了神经母细胞瘤的生长。我们通过与 IKKβ 的相互作用提供了 miR-429 作为肿瘤抑制因子的重要见解,IKKβ 是激活 NF-κB 核转运的 IKK 复合物的催化亚基。我们的研究结果表明,miR-429 可能是治疗神经母细胞瘤的新靶点。它是 IKK 复合物的催化亚基,可激活 NF-κB 核转运。我们的研究结果表明,miR-429 可能是治疗神经母细胞瘤的新靶点。它是 IKK 复合物的催化亚基,可激活 NF-κB 核转运。我们的研究结果表明,miR-429 可能是治疗神经母细胞瘤的新靶点。
更新日期:2020-02-13
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