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ErbB2-intronic MicroRNA-4728: a novel tumor suppressor and antagonist of oncogenic MAPK signaling
- Source :
- Cell Death & Disease
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Although the role of the ErbB2/HER2 oncogene in cancers has been extensively studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir-4728, was recently found within an intron of the ErbB2 gene. However, the function and clinical relevance of this intronic miRNA are completely unknown. Here, we demonstrate that mir-4728 is a negative regulator of MAPK signaling through directly targeting the ERK upstream kinase MST4 and exerts numerous tumor-suppressive properties in vitro and in animal models. Importantly, our patient sample study shows that mir-4728 was under-expressed in breast tumors compared with normal tissue, and loss of mir-4728 correlated with worse overall patient survival. These results strongly suggest that mir-4728 is a tumor-suppressive miRNA that controls MAPK signaling through targeting MST4, revealing mir-4728’s significance as a potential prognostic factor and target for therapeutic intervention in cancer. Moreover, this study represents a conceptual advance by providing strong evidence that a tumor-suppressive miRNA can antagonize the canonical signaling of its host oncogene.
- Subjects :
- MAPK/ERK pathway
Cancer Research
MAP Kinase Signaling System
Receptor, ErbB-2
Immunology
Breast Neoplasms
Biology
Mitogen-activated protein kinase kinase
Bioinformatics
law.invention
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
law
Cell Line, Tumor
microRNA
Humans
Genes, Tumor Suppressor
Cell Proliferation
030304 developmental biology
Mitogen-Activated Protein Kinase Kinases
Regulation of gene expression
0303 health sciences
Oncogene
Kinase
Cell Biology
Introns
3. Good health
Gene Expression Regulation, Neoplastic
MicroRNAs
030220 oncology & carcinogenesis
Cancer research
Suppressor
Female
Original Article
Signal transduction
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....64b2ecf3e0785aee5c808813970b991e