MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth
2017-07
发表期刊PLOS GENETICS
ISSN1553-7404
卷号13期号:7
发表状态已发表
DOI10.1371/journal.pgen.1006896
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.
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收录类别SCI
语种英语
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]
WOS研究方向Genetics & Heredity
WOS类目Genetics & Heredity
WOS记录号WOS:000406615300033
出版者PUBLIC LIBRARY SCIENCE
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
原始文献类型Article
通讯作者Miao, Lingling ; Ren, Jin
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2902
专题生命科学与技术学院
生命科学与技术学院_特聘教授组_任进组
生命科学与技术学院_硕士生
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
第一作者单位生命科学与技术学院
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).
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