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微小 RNA-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。

MicroRNA-429 inhibits neuroblastoma cell proliferation, migration and invasion via the NF-κB pathway.

机构信息

1Department of Pediatric Surgery, the Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, 266000 Shandong China.

2Department of Operation Room, the Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266000 Shandong China.

出版信息

Cell Mol Biol Lett. 2020 Feb 13;25:5. doi: 10.1186/s11658-020-0202-9. eCollection 2020.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

MicroRNAs(miRNAs 或 miRs)可以参与神经母细胞瘤的发生和发展。许多研究表明 miR-429 可以参与肿瘤的发生。然而,miR-429 介导的神经母细胞瘤进展的机制在很大程度上仍不清楚。

方法

采用集落形成和细胞凋亡实验检测 miR-429 对细胞增殖的影响。划痕实验和 Transwell 实验检测 miR-429 对细胞迁移的影响。采用 Western blot 和荧光素酶报告基因实验验证 miR-429 的靶基因。通过 miR-429 过表达的裸鼠异种移植模型评估其对肿瘤生长的影响。

结果

我们的研究结果表明,miR-429 在神经母细胞瘤细胞系中表达下调。还发现它可以诱导这些细胞系中的细胞凋亡和抑制增殖。miR-429 可以与 IKKβ mRNA 的 3'-UTR 结合,过表达 IKKβ 可以逆转细胞增殖,阻断 miR-429 的作用。此外,miR-429 过表达抑制了我们的裸鼠异种移植模型中的神经母细胞瘤生长。

结论

我们通过与 IKKβ 的相互作用提供了关于 miR-429 作为肿瘤抑制因子的重要见解,IKKβ 是 IKK 复合物的催化亚基,可激活 NF-κB 核转运。我们的结果表明,miR-429 可能是神经母细胞瘤治疗的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90bf/7020518/aebfa24b06ed/11658_2020_202_Fig1_HTML.jpg

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