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橄榄苦苷通过HIF1α抑制的微小RNA-519d下调PDRG1，增强鼻咽癌的放射敏感性。

Oleuropein enhances radiation sensitivity of nasopharyngeal carcinoma by downregulating PDRG1 through HIF1α-repressed microRNA-519d.

作者信息

Xu Ting, Xiao Dajiang

机构信息

Department of Otorhinolarynogology, The Second People's Hospital of Wuxi, Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China.

出版信息

J Exp Clin Cancer Res. 2017 Jan 5;36(1):3. doi: 10.1186/s13046-016-0480-2.

DOI:10.1186/s13046-016-0480-2
PMID:28057028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5216549/
Abstract

BACKGROUND

Oleuropein (OL) is a well-known anti-oxidative agent and is shown to reduce the hypoxia-inducible factor 1 α (HIF1α) protein expression after radiation. The current study investigated the effects of OL on radiation response in nasopharyngeal carcinoma (NPC).

METHODS

Colony formation assay was performed to compare the radiation response in vitro. Xenograft mouse model was used to study the OL effects on radiation in vivo. Chromatin immunoprecipitation and luciferase reporter assays were performed to identify the relations among HIF1α, miR-519d and PDRG1. Stable HIF1α or PDRG1 overexpression, and miR-519d downregulation were performed to test the radiation response both in vitro and in vivo.

RESULTS

OL strongly enhanced radiosensitivity of NPC cells both in vitro and in vivo. Chromatin immunoprecipitation and luciferase reporter assays suggested miR-519d was a direct target of HIF1α, and PDRG1 was a direct target of miR-519d. Overexpression of HIF1α or PDRG1, and downregulation of miR-519d abolished the radiation sensitizing effects of OL.

CONCLUSION

Our study hereby demonstrates OL is a radiation sensitizing agent in NPC both in vivo and in vitro. OL treatment reduces the activity of HIF1α-miR-519d-PDRG1 pathway, which is essential to the radiosensitizing effects of OL.

摘要

背景

橄榄苦苷（OL）是一种著名的抗氧化剂，已显示其能在辐射后降低缺氧诱导因子1α（HIF1α）蛋白表达。本研究调查了OL对鼻咽癌（NPC）辐射反应的影响。

方法

进行集落形成试验以比较体外辐射反应。采用异种移植小鼠模型研究OL对体内辐射的影响。进行染色质免疫沉淀和荧光素酶报告基因试验以确定HIF1α、miR-519d和PDRG1之间的关系。进行稳定的HIF1α或PDRG1过表达以及miR-519d下调试验，以测试体外和体内的辐射反应。

结果

OL在体外和体内均强烈增强了NPC细胞的放射敏感性。染色质免疫沉淀和荧光素酶报告基因试验表明，miR-519d是HIF1α的直接靶点，PDRG1是miR-519d的直接靶点。HIF1α或PDRG1的过表达以及miR-519d的下调消除了OL的辐射增敏作用。

结论

我们的研究在此证明，OL在体内和体外均是NPC的辐射增敏剂。OL治疗降低了HIF1α-miR-519d-PDRG1通路的活性，这对OL的辐射增敏作用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3a848c9d2e89/13046_2016_480_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/16e6037fb3ca/13046_2016_480_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/a67f577e2313/13046_2016_480_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3829706260a1/13046_2016_480_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/31e509c5623e/13046_2016_480_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3fd7267b6c32/13046_2016_480_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/851b30be8efd/13046_2016_480_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/96936eaf7805/13046_2016_480_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3a848c9d2e89/13046_2016_480_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/16e6037fb3ca/13046_2016_480_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/a67f577e2313/13046_2016_480_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3829706260a1/13046_2016_480_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/31e509c5623e/13046_2016_480_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3fd7267b6c32/13046_2016_480_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/851b30be8efd/13046_2016_480_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/96936eaf7805/13046_2016_480_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0675/5216549/3a848c9d2e89/13046_2016_480_Fig8_HTML.jpg

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