MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth

doi:10.1371/journal.pgen.1006896

	MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth
	Pu, Mengfan1,2,3 ; Li, Chenggang 1,3; Qi, Xinming 1,3; Chen, Jing 1,3; Wang, Yizheng 4; Gao, Lulu 1,3; Miao, Lingling 1,3; Ren, Jin1,3
	2017-07
发表期刊	PLOS GENETICS
ISSN	1553-7404
卷号	13 期号:7
发表状态	已发表
DOI	10.1371/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).