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

19 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 - 2016 Jun 1

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Interleukin-8
Squamous Cell Carcinoma
Suppressor of Cytokine Signaling Proteins
Cell Movement
Janus Kinases
Transducers
Matrix Metalloproteinases
Proteins
Down-Regulation
Phosphorylation
Cytokines
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Peng, Hsuan Yu ; Jiang, Shih Sheng ; Hsiao, Jenn-Ren ; Hsiao, Michael ; Hsu, Yuan Ming ; Wu, Guan Hsun ; Chang, Wei Min ; Chang, Jang-Yang ; Jin, Shiow Lian Catherine ; Shiah, Shine Gwo. / IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma. In: Molecular Oncology. 2016 ; Vol. 10, No. 6. pp. 895-909.
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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.",
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IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma. / Peng, Hsuan Yu; Jiang, Shih Sheng; Hsiao, Jenn-Ren; Hsiao, Michael; Hsu, Yuan Ming; Wu, Guan Hsun; Chang, Wei Min; Chang, Jang-Yang; Jin, Shiow Lian Catherine; Shiah, Shine Gwo.

In: Molecular Oncology, Vol. 10, No. 6, 01.06.2016, p. 895-909.

Research output: Contribution to journalArticle

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AU - Peng, Hsuan Yu

AU - Jiang, Shih Sheng

AU - Hsiao, Jenn-Ren

AU - Hsiao, Michael

AU - Hsu, Yuan Ming

AU - Wu, Guan Hsun

AU - Chang, Wei Min

AU - Chang, Jang-Yang

AU - Jin, Shiow Lian Catherine

AU - Shiah, Shine Gwo

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AB - 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.

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