IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma

Hsuan Yu Peng, Shih Sheng Jiang, Jenn Ren Hsiao, Michael Hsiao, Yuan Ming Hsu, Guan Hsun Wu, Wei Min Chang, Jang Yang Chang, Shiow Lian Catherine Jin, Shine Gwo Shiah

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)895-909
Number of pages15
JournalMolecular Oncology
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Keywords

  • IL-8
  • Invasion
  • MicroRNA
  • Oral squamous cell carcinoma
  • SOCS2

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    Peng, H. Y., Jiang, S. S., Hsiao, J. R., Hsiao, M., Hsu, Y. M., Wu, G. H., Chang, W. M., Chang, J. Y., Jin, S. L. C., & Shiah, S. G. (2016). IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma. Molecular Oncology, 10(6), 895-909. https://doi.org/10.1016/j.molonc.2016.03.001