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Updated: Apr 19, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Involvement of aberrant miR-139/Jun feedback loop in human gastric cancer
Yan Zhang1, Wen-Long Shen1, Ming-Lei Shi1
1Institute of Biotechnology, Beijing 100071, China.
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.
Insights
A novel feedback loop between microRNA-139 (miR-139) and its target Jun was identified. Aberrant miR-139/Jun signaling drives gastric cancer, with miR-139 showing therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in maintaining tissue homeostasis.
- Disruption of miRNA-target feedback loops is implicated in human tumorigenesis.
- Understanding these regulatory networks is vital for cancer research.
Purpose of the Study:
- To identify and characterize a novel feedback loop involving miRNAs and their targets.
- To investigate the role of this feedback loop in human gastric cancer development.
- To explore the therapeutic potential of targeting this loop in cancer treatment.
Main Methods:
- Identification of a negative feedback loop between miR-139 and Jun.
- Analysis of the regulatory interaction between miR-139 and Jun's 3'-UTR and upstream elements.
- Examination of miR-139 and Jun expression levels in human gastric cancer tissues.
- Functional assays in gastric cancer cells to assess the impact of miR-139 restoration.
Main Results:
- A novel negative feedback loop between miR-139 and its oncogenic target Jun was identified.
- miR-139 directly targets Jun, while Jun induces miR-139 expression.
- This loop is aberrantly regulated in human gastric cancer, with decreased miR-139 and increased Jun.
- Restoring miR-139 suppressed gastric cancer cell proliferation, migration, and tumor growth by targeting Jun.
Conclusions:
- The aberrant miR-139/Jun negative feedback loop is a key factor in human gastric cancer development.
- miR-139 acts as a tumor suppressor in gastric cancer by targeting Jun.
- miR-139 represents a potential therapeutic target for gastric cancer and possibly other cancers.
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