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微小RNA-30a调控CAGE和p53的表达并调节对抗癌药物的反应。

miR-30a Regulates the Expression of CAGE and p53 and Regulates the Response to Anti-Cancer Drugs.

作者信息

Park Deokbum, Kim Hyuna, Kim Youngmi, Jeoung Dooil

机构信息

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.

出版信息

Mol Cells. 2016 Apr 30;39(4):299-309. doi: 10.14348/molcells.2016.2242. Epub 2016 Feb 25.

DOI:10.14348/molcells.2016.2242
PMID:26912082
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4844936/
Abstract

We have previously reported the role of miR-217 in anti-cancer drug-resistance. miRNA array and miRNA hybridization analysis predicted miR-30a-3p as a target of miR-217. miR-30a-3p and miR-217 formed a negative feedback loop and regulated the expression of each other. Ago1 immunoprecipitation and co-localization analysis revealed a possible interaction between miR-30a-3p and miR-217. miR-30a-3p conferred resistance to anti-cancer drugs and enhanced the invasion, migration, angiogenic, tumorigenic, and metastatic potential of cancer cells in CAGE-dependent manner. CAGE increased the expression of miR-30a-3p by binding to the promoter sequences of miR-30a-3p, suggesting a positive feedback loop between CAGE and miR-30a-3p. miR-30a-3p decreased the expression of p53, which showed the binding to the promoter sequences of miR-30a-3p and CAGE in anti-cancer drug-sensitive cancer cells. Luciferase activity assays showed that p53 serves as a target of miR-30a. Thus, the miR-30a-3p-CAGE-p53 feedback loop serves as a target for overcoming resistance to anti-cancer drugs.

摘要

我们之前报道了miR-217在抗癌药物耐药性中的作用。miRNA阵列和miRNA杂交分析预测miR-30a-3p是miR-217的一个靶点。miR-30a-3p和miR-217形成了一个负反馈环并相互调节表达。AGO1免疫沉淀和共定位分析揭示了miR-30a-3p与miR-217之间可能存在的相互作用。miR-30a-3p赋予癌细胞对抗癌药物的耐药性,并以依赖CAGE的方式增强癌细胞的侵袭、迁移、血管生成、致瘤和转移潜能。CAGE通过与miR-30a-3p的启动子序列结合来增加miR-30a-3p的表达,这表明CAGE与miR-30a-3p之间存在正反馈环。miR-30a-3p降低了p53的表达,在抗癌药物敏感的癌细胞中,p53显示出与miR-30a-3p和CAGE的启动子序列结合。荧光素酶活性测定表明p53是miR-30a的一个靶点。因此,miR-30a-3p-CAGE-p53反馈环可作为克服抗癌药物耐药性的一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cc8/4844936/d08c6e75577f/molce-39-4-299f7.jpg
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