A feedback regulation between miR-145 and DNA methyltransferase 3b in prostate cancer cell and their responses to irradiation

被引:70
作者
Xue, Gang [1 ,2 ]
Ren, Zhenxin [1 ]
Chen, Yaxiong [1 ]
Zhu, Jiayun [1 ]
Du, Yarong [1 ]
Pan, Dong [1 ,2 ]
Li, Xiaoman [1 ,2 ]
Hu, Burong [1 ]
机构
[1] Chinese Acad Sci, Inst Modern Phys, Dept Space Radiobiol, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
基金
中国国家自然科学基金;
关键词
Feedback loop; miR-145; DNMT3b; Prostate cancer; Radiosensitivity; TUMOR-SUPPRESSOR; EPIGENETIC REGULATION; DOWN-REGULATION; LUNG-CANCER; METHYLATION; MICRORNAS; RADIATION; GROWTH; DNMT3B; GENE;
D O I
10.1016/j.canlet.2015.02.046
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It is believed that epigenetic modification plays roles in cancer initiation and progression. Both microRNA and DNA methyltransferase are epigenetic regulation factors. It was found that miR-145 upregulates while DNMT3b downregulates in PD cells. Presence of any negative correlationship and their response to irradiation were investigated in the current study. We found that miR-145 downregulated DNMT3b expression by directly targeting the 3 '-UTR of DNMT3b mRNA and knockdown of DNMT3b increased expression of miR-145 via CpG island promoter hypomethylation, suggesting that there is a crucial crosstalk between miR-145 and DNMT3b via a double-negative feedback loop. Responses of the miR-145 and DNMT3b to irradiation are a negative correlation. We also found that either overexpression of miR-145 or knockdown of DNMT3b sensitized prostate cancer cells to X-ray radiation. Our findings enrich the complex relationships between miRNA and DNMTs in carcinogenesis and irradiation stress. It also sheds light on the potential combination of ionizing radiation and epigenetic regulation in prostate cancer therapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:121 / 127
页数:7
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