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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2012, Vol. 17 ›› Issue (7): 744-749.

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The role of downregulation of insulin receptor substrate 1 in the invasion and metastasis of head and neck squamous cell carcinoma

LUO Xuan1, HUANG Wen-bin2, ZHAI Su-lan1, MA Zhuo1, LI Ping1, WANG Xue-rong1   

  1. 1Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
    2Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
  • Received:2012-02-28 Revised:2012-06-12 Published:2012-07-17

Abstract: AIM: To explore the role of insulin receptor substrate 1 (IRS-1) in the invasion and metastasis of head and neck squamous cell carcinoma(HNSCC) and potential mechanism. METHODS: IRS-1 mRNA expression in the metastatic lymph node and corresponding primary tumour tissues of HNSCC patients, in highly and poorly metastatic HNSCC cells were detec-ted byqRT-PCR. miR-9 and U6 expression were measured by the TaqMan microRNA qPCR. IRS-1 expression was downregulated by using siRNA. The effect of IRS-1 on cell invasive potency was examined by transwell invasion assay after IRS-1 interference. E-cadherin and vimentin were detected by qRT-PCR and Western blot. Cell survival rate was examined by SRB assay. RESULTS: IRS-1 mRNA expression decreased in the metastatic lymph node tumor tissues compared to primary tumor tissues of HNSCC patients(P<0.05). As well, its expression levels were lower in highly metastatic HNSCC cells compared to its parental poorly metastatic cells(P<0.05). IRS-1 knockdown promoted invasion of poorly metastatic 686LN cells and induced EMT in parallel with upregulation of miR-9 expression. CONCLUSION: Downregulation of IRS-1 may promote invasion and metastasis of head and neck squamous cell carcinoma by epithelial-mesenchymal transition and upregulating miR-9 expression.

Key words: Insulin receptor substrate 1 (IRS-1), Head and neck squamous cell carcinoma (HNSCC), Metastasis, E-cadherin, miR-9

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