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

Hsuan-Yu Peng1, Shih-Sheng Jiang2, Jenn-Ren Hsiao3

  • 1National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Department of Life Sciences, National Central University, Taoyuan, Taiwan.

Molecular Oncology
|April 4, 2016
PubMed

Insights

Suppressor of cytokine signaling 2 (SOCS2) is downregulated in oral cancer, with miR-424-5p promoting cancer progression by targeting SOCS2. Inactivating miR-424-5p may offer a new oral cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Suppressor of cytokine signaling (SOCS) proteins regulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.
  • Dysregulated SOCS expression in cancer can lead to sustained STAT activation, a mechanism poorly understood in oral squamous cell carcinoma (OSCC).

Purpose of the Study:

  • To investigate the role of SOCS2 and miR-424-5p in oral squamous cell carcinoma (OSCC).
  • To elucidate the regulatory relationship between miR-424-5p, SOCS2, and the IL-8/STAT5 signaling axis in OSCC.

Main Methods:

  • Quantitative analysis of SOCS2 and miR-424-5p expression in OSCC patients.
  • Luciferase reporter assays to confirm direct targeting of SOCS2 by miR-424-5p.
  • In vitro experiments assessing the effects of SOCS2 restoration and miR-424-5p inhibition on cell migration and invasion.
  • Analysis of IL-8 induced signaling pathways (STAT5 and NF-κB).

Main Results:

  • SOCS2 protein was significantly downregulated in OSCC, inversely correlated with miR-424-5p expression.
  • SOCS2 was identified as a direct target of miR-424-5p, and its restoration blocked miR-424-5p-induced STAT5 phosphorylation, MMPs expression, migration, and invasion.
  • miR-424-5p expression was induced by IL-8 via STAT5 activation.
  • Antagomir-mediated inactivation of miR-424-5p inhibited IL-8-induced cell migration and invasion.

Conclusions:

  • The IL-8/STAT5/SOCS2 feedback loop, mediated by STAT5-dependent miR-424-5p expression, plays a crucial role in OSCC progression.
  • Targeting miR-424-5p with antagomirs presents a potential therapeutic strategy for OSCC.
Keywords:
IL-8InvasionOral squamous cell carcinomaSOCS2microRNA

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