Molecular oncology, 2016-06, Vol.10 (6), p.895-909
2016
Details
- Autor(en) / Beteiligte
- Titel
- IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma
- Ist Teil von
- Molecular oncology, 2016-06, Vol.10 (6), p.895-909
- Ort / Verlag
- United States: Elsevier B.V
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Dysregulation of SOCS protein expression in cancers can be one of the mechanisms that maintain STAT activation, but this mechanism is still poorly understood in oral squamous cell carcinoma (OSCC). Here, we report that SOCS2 protein is significantly downregulated in OSCC patients and its levels are inversely correlated with miR-424-5p expression. We identified the SOCS2 protein, which modulates STAT5 activity, as a direct target of miR-424-5p. The miR-424-5p-induced STAT5 phosphorylation, matrix metalloproteinases (MMPs) expression, and cell migration and invasion were blocked by SOCS2 restoration, suggesting that miR-424-5p exhibits its oncogenic activity through negatively regulating SOCS2 levels. Furthermore, miR-424-5p expression could be induced by the cytokine IL-8 primarily through enhancing STAT5 transcriptional activity rather than NF-κB signaling. Antagomir-mediated inactivation of miR-424-5p prevented the IL-8-induced cell migration and invasion, indicating that miR-424-5p is required for IL-8-induced cellular invasiveness. Taken together, these data indicate that STAT5-dependent expression of miR-424-5p plays an important role in mediating IL-8/STAT5/SOCS2 feedback loop, and scavenging miR-424-5p function using antagomir may have therapeutic potential for the treatment of OSCC. •miR-424-5p is overexpressed in OSCC.•miR-424-5p directly targets SOCS2, leading to increased cell migration and invasion.•STAT5 activation is required for IL-8-mediated miR-424-5p transcription.•miR-424-5p plays an important role in mediating IL-8/STAT5/SOCS2 feedback loop.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1574-7891eISSN: 1878-0261DOI: 10.1016/j.molonc.2016.03.001Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5423170
- Format
- –
- Schlagworte
- Binding sites, Cancer therapies, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, Cell adhesion & migration, Cell growth, Cell Line, Tumor, Cell migration, Cell Movement, Cytokines, Epidermal growth factor, Feedback, Gene expression, Gene Expression Regulation, Neoplastic, Humans, IL-8, Interleukin-8 - metabolism, Invasion, Invasiveness, Janus kinase, Kinases, Matrix metalloproteinase, microRNA, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, Mouth - metabolism, Mouth - pathology, Mouth Neoplasms - genetics, Mouth Neoplasms - metabolism, Mouth Neoplasms - pathology, Neoplasm Invasiveness - genetics, Neoplasm Invasiveness - pathology, Oral cancer, Oral squamous cell carcinoma, Phosphorylation, Proteins, Signal Transduction, SOCS2, Squamous cell carcinoma, Stat5 protein, STAT5 Transcription Factor - metabolism, Suppressor of Cytokine Signaling Proteins - genetics, Suppressor of Cytokine Signaling Proteins - metabolism, Transcription