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

研究成果: Article

20 引文 (Scopus)

摘要

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.

原文English
頁(從 - 到)895-909
頁數15
期刊Molecular Oncology
10
發行號6
DOIs
出版狀態Published - 2016 六月 1

指紋

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

引用此文

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. 於: Molecular Oncology. 2016 ; 卷 10, 編號 6. 頁 895-909.
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title = "IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma",
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.",
author = "Peng, {Hsuan Yu} and Jiang, {Shih Sheng} and Hsiao, {Jenn Ren} and Michael Hsiao and Hsu, {Yuan Ming} and Wu, {Guan Hsun} and Chang, {Wei Min} and Chang, {Jang Yang} and Jin, {Shiow Lian Catherine} and Shiah, {Shine Gwo}",
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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.

於: Molecular Oncology, 卷 10, 編號 6, 01.06.2016, p. 895-909.

研究成果: Article

TY - JOUR

T1 - IL-8 induces miR-424-5p expression and modulates SOCS2/STAT5 signaling pathway in oral squamous cell carcinoma

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

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

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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