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Biochim Biophys Acta. 2015 Feb;1853(2):481-8. doi: 10.1016/j.bbamcr.2014.12.002. Epub 2014 Dec 10.

Involvement of aberrant miR-139/Jun feedback loop in human gastric cancer.

Author information

1
Institute of Biotechnology, Beijing 100071, China.
2
Institute of Biotechnology, Beijing 100071, China; School of Life Science, Anhui University, Hefei 230601, China.
3
Institute of Biotechnology, Beijing 100071, China. Electronic address: Sunqiang1975@126.com.
4
Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China.
5
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China. Electronic address: yangx@bmi.ac.cn.
6
Institute of Biotechnology, Beijing 100071, China. Electronic address: zhaozh@bmi.ac.cn.

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.

KEYWORDS:

Feedback loop; Gastric cancer; Jun; MiR-139

PMID:
25499265
DOI:
10.1016/j.bbamcr.2014.12.002
[Indexed for MEDLINE]
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