Oleuropein enhances radiation sensitivity of nasopharyngeal carcinoma by downregulating PDRG1 through HIF1α-repressed microRNA-519d.
Oleuropein enhances radiation sensitivity of nasopharyngeal carcinoma by downregulating PDRG1 through HIF1α-repressed microRNA-519d.
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DOI：
10.1186/s13046-016-0480-2
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发表时间：
2017-01-05
期刊：
影响因子：
--
通讯作者：
Xiao D
中科院分区：
文献类型：
--
作者：
Xu T;Xiao D
橄榄苦苷（OL）是一种众所周知的抗氧化剂，可以降低辐射后缺氧诱导因子1α (HIF1α)蛋白的表达。本研究探讨OL对鼻咽癌（NPC）放射反应的影响。采用菌落形成试验比较体外辐照反应。采用异种移植小鼠模型研究OL对体内辐射的影响。采用染色质免疫沉淀和荧光素酶报告基因检测来鉴定HIF1α、miR-519d和PDRG1之间的关系。通过稳定的HIF1α或PDRG1过表达和miR-519d下调来检测体外和体内的辐射反应。OL在体外和体内均能增强鼻咽癌细胞的放射敏感性。染色质免疫沉淀和荧光素酶报告基因检测表明，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的下调可消除OL的辐射增敏作用。我们的研究表明OL在体内和体外都是鼻咽癌的辐射增敏剂。OL处理降低了HIF1α-miR-519d-PDRG1通路的活性，这对OL的放射增敏作用至关重要。
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). 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. 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. 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.
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影响因子：
6.1
作者：
de la Puerta, R;Domínguez, MEM;Hoult, JRS
通讯作者：
Hoult, JRS
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
DOI：
10.1186/1748-717x-5-100
发表时间：
2010-11-01
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Jiang P;Rao EY;Meng N;Zhao Y;Wang JJ
通讯作者：
Wang JJ
影响因子：
3.6
作者：
Babar, Imran A.;Czochor, Jennifer;Slack, Frank J.
通讯作者：
Slack, Frank J.
DOI：
10.1016/j.bbrc.2005.06.161
发表时间：
2005-09-02
影响因子：
3.1
作者：
Hamdi, HK;Castellon, R
通讯作者：
Castellon, R