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微小 RNA-1247 通过直接靶向神经母细胞瘤中的 ZNF346 抑制细胞增殖。

MicroRNA-1247 inhibits cell proliferation by directly targeting ZNF346 in childhood neuroblastoma.

机构信息

Department of Neonatology, The First People's Hospital of Jingzhou, No. 8 Hangkong Road, Shashi District, Jingzhou, 434000, Hubei, China.

Department of Editor, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan, China.

出版信息

Biol Res. 2018 May 24;51(1):13. doi: 10.1186/s40659-018-0162-y.

DOI:10.1186/s40659-018-0162-y
PMID:29793538
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5966945/
Abstract

BACKGROUND

Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro.

METHODS/RESULTS: We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be downregulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells.

CONCLUSIONS

Our findings suggested miR-1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB.

摘要

背景

神经母细胞瘤(NB)是儿童最常见的颅外实体瘤。越来越多的证据表明 microRNAs(miRs)在 NB 的发生发展中起重要作用。本研究旨在体外研究 miR-1247 在 NB 中的生物学功能。

方法/结果:通过定量 PCR 分析发现 miR-1247 在 NB 组织和细胞中下调。通过 MTT、集落形成实验和流式细胞术分析,发现 gain-和 loss-of-function 研究表明 miR-1247 可显著抑制 NB 细胞的增殖,并诱导细胞周期 G0/G1 期阻滞和细胞凋亡。荧光素酶报告基因实验表明 ZNF346 是 miR-1247 的靶基因,其表达可通过 miR-1247 过表达下调,Western blot 验证了这一结果。此外,siRNA 下调 ZNF346 的表达与 miR-1247 过表达在 NB 细胞中具有相似的作用。

结论

我们的研究结果表明,miR-1247 可直接靶向抑制 ZNF346 的表达,从而抑制 NB 的进展,这可能是一种针对 NB 的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/0d4771e55572/40659_2018_162_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/97f3c60fa44b/40659_2018_162_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/70711edde7e4/40659_2018_162_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/8f46ffb6f8b4/40659_2018_162_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/3a0f3006a710/40659_2018_162_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/78aa718f9489/40659_2018_162_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/0d4771e55572/40659_2018_162_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/97f3c60fa44b/40659_2018_162_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/70711edde7e4/40659_2018_162_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/8f46ffb6f8b4/40659_2018_162_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/3a0f3006a710/40659_2018_162_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/78aa718f9489/40659_2018_162_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17a5/5966945/0d4771e55572/40659_2018_162_Fig6_HTML.jpg

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