Hypoxia-inducible miR-182 enhances HIF1 alpha signaling via targeting PHD2 and FIH1 in prostate cancer
文献类型：期刊论文
| 作者 | Li, Yan; Zhang, Duo; Wang, Xiaoyun; Yao, Xuan; Ye, Cheng; Zhang, Shengjie; Wang, Hui（王慧）; Chang, Cunjie; Xia, Hongfeng; Wang, Yu-cheng |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2015 |
| 卷号 | 5期号:0页码:12495 |
| 通讯作者 | Yan, J (reprint author), Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China. |
| 英文摘要 | Activation of hypoxia-inducible factor 1 alpha (HIF1 alpha) controls the transcription of genes governing angiogenesis under hypoxic condition during tumorigenesis. Here we show that hypoxia-responsive miR-182 is regulated by HIF1 alpha at transcriptional level. Prolyl hydroxylase domain enzymes (PHD) and factor inhibiting HIF-1 (FIH1), negative regulators of HIF1 signaling, are direct targets of miR-182. Overexpression of miR-182 in prostate cancer cells led to a reduction of PHD2 and FIH1 expression and an increase in HIF1 alpha level either under normoxic or hypoxic condition. Consistently, inhibition of miR-182 could increase PHD2 and FIH1 levels, thereby reducing the hypoxia-induced HIF1 alpha expression. Matrigel plug assay showed that angiogenesis was increased by miR-182 overexpression, and vice versa. miR-182 overexpression in PC-3 prostate cancer xenografts decreased PHD2 and FIH1 expression, elevated HIF1 alpha protein levels, and increased tumor size. Lastly, we revealed that the levels of both miR-182 and HIF1 alpha were elevated, while the expression PHD2 and FIH1 was downregulated in a mouse model of prostate cancer. Together, our results suggest that the interplay between miR-182 and HIF1 alpha could result in a sustained activation of HIF1 alpha pathway, which might facilitate tumor cell adaption to hypoxic stress during prostate tumor progression. |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | GENE-EXPRESSION ; FACTOR 1-ALPHA ; TUMOR ANGIOGENESIS ; CELLS ; CARCINOMA ; MIR-210 ; HIF ; HIF-1-ALPHA ; SUPPRESSION ; METASTASIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000358423500001 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/328]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_营养与癌症研究组 |
| 推荐引用方式 GB/T 7714 | Li, Yan,Zhang, Duo,Wang, Xiaoyun,et al. Hypoxia-inducible miR-182 enhances HIF1 alpha signaling via targeting PHD2 and FIH1 in prostate cancer[J]. SCIENTIFIC REPORTS,2015,5(0):12495. |
| APA | Li, Yan.,Zhang, Duo.,Wang, Xiaoyun.,Yao, Xuan.,Ye, Cheng.,...&Ying, Hao.(2015).Hypoxia-inducible miR-182 enhances HIF1 alpha signaling via targeting PHD2 and FIH1 in prostate cancer.SCIENTIFIC REPORTS,5(0),12495. |
| MLA | Li, Yan,et al."Hypoxia-inducible miR-182 enhances HIF1 alpha signaling via targeting PHD2 and FIH1 in prostate cancer".SCIENTIFIC REPORTS 5.0(2015):12495. |
入库方式： OAI收割
来源：上海营养与健康研究所
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