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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.

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Institute of Biotechnology, Beijing 100071, China.
Institute of Biotechnology, Beijing 100071, China; School of Life Science, Anhui University, Hefei 230601, China.
Institute of Biotechnology, Beijing 100071, China. Electronic address:
Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China.
State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China. Electronic address:
Institute of Biotechnology, Beijing 100071, China. Electronic address:


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.


Feedback loop; Gastric cancer; Jun; MiR-139

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