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miR-199a-3p 通过靶向 AK4 影响骨肉瘤的多药耐药性。

MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4.

机构信息

Department of orthopaedic surgery, the third people's hospital of Hefei, Hefei, 230031, Anhui, China.

出版信息

BMC Cancer. 2018 Jun 4;18(1):631. doi: 10.1186/s12885-018-4460-0.

DOI:10.1186/s12885-018-4460-0
PMID:29866054
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5987492/
Abstract

BACKGROUND

MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer.

METHODS

We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance.

RESULTS

The AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells.

CONCLUSIONS

Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance.

摘要

背景

MicroRNAs (miRNAs) 在调节各种生物过程中起着至关重要的作用。miRNAs 的失调可能导致严重的人类疾病，包括癌症。

方法

我们通过 qRT-PCR、western blot 和荧光素酶报告基因实验来检测腺苷酸激酶 4 (AK4) 是否是 miR-199a-3p 的靶基因。通过上调或下调 miR-199a-3p 和/或 AK4 基因，使用耐药谱分析来检测它们在 OS 多药耐药中的作用。我们进一步预测了 miR-199a-3p 介导的 OS 耐药性涉及的潜在信号通路。

结果

AK4 基因是 miR-199a-3p 的靶基因之一，与 miR-199a-3p 对 OS 耐药性的影响呈负相关。此外，NF-кB 信号通路的活性在 OS 细胞中 miR-199a-3p 水平的强制变化下发生了明显改变。

结论

我们的数据表明，miR-199a-3p 及其靶基因 AK4 与 OS 耐药性呈负相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/f5edb07eb7f8/12885_2018_4460_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/21f8f65c2219/12885_2018_4460_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/abe9fc3d3411/12885_2018_4460_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/41c26efacbb8/12885_2018_4460_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/aaedfa4c006d/12885_2018_4460_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/a164d3fc0d33/12885_2018_4460_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/f5edb07eb7f8/12885_2018_4460_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/21f8f65c2219/12885_2018_4460_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/abe9fc3d3411/12885_2018_4460_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/41c26efacbb8/12885_2018_4460_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/aaedfa4c006d/12885_2018_4460_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/a164d3fc0d33/12885_2018_4460_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5558/5987492/f5edb07eb7f8/12885_2018_4460_Fig6_HTML.jpg

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