MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth
文献类型：期刊论文
| 作者 | Pu, Mengfan1,2,3; Li, Chenggang1,3; Qi, Xinming1,3 ; Chen, Jing1,3; Wang, Yizheng4; Gao, Lulu1,3; Miao, Lingling1,3; Ren, Jin1,3
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| 刊名 | PLOS GENETICS
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| 出版日期 | 2017-07 |
| 卷号 | 13期号:7 |
| ISSN号 | 1553-7404 |
| DOI | 10.1371/journal.pgen.1006896 |
| 文献子类 | Article |
| 英文摘要 | MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post-transcriptional gene silencing (PTGS) and function in a vast range of biological events including cancer development. Most miRNAs pair to the target sites through seed region near the 5' end, leading to mRNA cleavage and/or translation repression. Here, we demonstrated a miRNA-induced dual regulation of heme oxygenase-1 (HO-1) via seed region and non-seed region, consequently inhibited tumor growth of NSCLC. We identified miR-1254 as a negative regulator inhibiting HO-1 translation by directly targeting HO-1 3' UTR via its seed region, and suppressing HO-1 transcription via non-seed region-dependent inhibition of transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1. MiR-1254 induced cell apoptosis and cell cycle arrest in human non-small cell lung carcinoma (NSCLC) cells by inhibiting the expression of HO-1, consequently suppressed NSCLC cell growth. Consistently with the in vitro studies, mouse xenograft studies validated that miR-1254 suppressed NSCLC tumor growth in vivo. Moreover, we found that HO-1 expression was inversely correlated with miR-1254 level in human NSCLC tumor samples and cell lines. Overall, these findings identify the dual inhibition of HO-1 by miR-1254 as a novel functional mechanism of miRNA, which results in a more effective inhibition of oncogenic mRNA, and leads to a tumor suppressive effect. |
| WOS关键词 | HEME OXYGENASE-1 GENE ; CELL LUNG-CANCER ; MICRORNA TARGET RECOGNITION ; MESSENGER-RNA ; MAMMALIAN-CELLS ; MIRNA MIMICS ; IN-VITRO ; SITES ; INDUCTION ; BINDING |
| 资助项目 | National Science and Technology Major Project[2012ZX09302-003] ; National Science and Technology Major Project[2012ZX09301-001-006] ; National Science and Technology Major Project[2015ZX09102005] ; National Health and Family Planning Commission of the People's Republic of China[00000000] |
| WOS研究方向 | Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:000406615300033 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272576]  |
| 专题 | 药物安全性评价中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Miao, Lingling; Ren, Jin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, Peoples R China; 4.Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pu, Mengfan,Li, Chenggang,Qi, Xinming,et al. MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth[J]. PLOS GENETICS,2017,13(7). |
| APA | Pu, Mengfan.,Li, Chenggang.,Qi, Xinming.,Chen, Jing.,Wang, Yizheng.,...&Ren, Jin.(2017).MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth.PLOS GENETICS,13(7). |
| MLA | Pu, Mengfan,et al."MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth".PLOS GENETICS 13.7(2017). |
入库方式： OAI收割
来源：上海药物研究所
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