title: Involvement of aberrant miR-139/Jun feedback loop in human gastric cancer.
abstract: Accumulating evidence indicates that some miRNAs could form feedback loops with their targets to fine-tune tissue homeostasis, while disruption of these loops constitutes an essential step towards human tumorigenesis. In this study, we report the identification of a novel negative feedback loop formed between miR-139 and its oncogenic target Jun. In this loop, miR-139 could inhibit Jun expression by targeting a conserved site on its 3'-UTR, whereas Jun could induce miR-139 expression in a dose dependent manner through a distant upstream regulatory element. Interestingly, aberration in this loop was found in human gastric cancer, where miR-139 was down-regulated and inversely correlated with Jun expression. Further functional analysis showed that restored expression of miR-139 in gastric cancer cells significantly induces apoptosis, and inhibits cell migration and proliferation as well as tumour growth through targeting Jun. Thus, our data strongly suggests a role of aberrant miR-139/Jun negative feedback loop in the development of human gastric cancer and miR-139 as a potential therapeutic target for gastric cancer. Given that miR-139 and Jun are deregulated in many cancers, our findings here might have broader implication in other types of human cancers.
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Shen
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Ming-Lei
authors.initials: ML
authors.lastname: Shi
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Le-Zhi
authors.initials: LZ
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Beijing 100071, China; School of Life Science, Anhui University, Hefei 230601, China.
authors.forename: Ling-Yue
authors.initials: LY
authors.lastname: Xing
authors.affiliation: Institute of Biotechnology, Beijing 100071, China.
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Luo
authors.affiliation: Institute of Biotechnology, Beijing 100071, China. Electronic address: Sunqiang1975@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China. Electronic address: yangx@bmi.ac.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Biotechnology, Beijing 100071, China. Electronic address: zhaozh@bmi.ac.cn.
authors.forename: Zhi-Hu
authors.initials: ZH
authors.lastname: Zhao
mesh_terms: D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun
keywords: Feedback loop; Gastric cancer; Jun; MiR-139