PURPOSE: To determine the interaction between insulin receptor substrate-1 (IRS-1) and miR-23a on the migration and invasion of non-small cell lung cancer (NSCLC) cells, and to examine IRS-1 expression in NSCLC tissues and its correlation with clinicopathologic characteristics. METHODS: The migration and invasion of A549 cells were measured using transwell assay. miR-23a levels were examined by quantitative reverse transcription-PCR and IRS-1 expression by Western blotting. The interaction between miR-23a and IRS-1 was examined by luciferase reporter assay. IRS-1 expression in 105 NSCLC specimens was determined by immunohistochemistry and its correlation with patient clinicopathologic characteristics was evaluated. RESULTS: Transwell assay revealed that miR-23a significantly promoted the migration and invasion of A549 cells with a 44.0 and 44.6 % increase in the number of migrated and invading cells, respectively. Luciferase assay showed that miR-23a markedly reduced luciferase activities of A549 cells co-transfected with plasmids overexpressing the 3' UTR of IRS-1 mRNA (P < 0.05). Co-transfection of A549 cells with miR-23a and plasmids overexpressing IRS-1 significantly reduced the increase in the number of migrated and invading cells mediated by miR-23a. Immunohistochemistry showed low IRS-1 expression in 26.7 % and high IRS-1 expression in 73.3 % of the NSCLC specimens. Kaplan-Meier analysis revealed that the overall survival and disease-free survival of NSCLC were markedly longer in patients with high IRS-1 expression than those with low IRS-1 expression (P = 0.002). Multivariate Cox regression analysis showed that IRS-1 was an independent prognostic factor for the overall survival of NSCLC patients (RR 0.413 CI 0.238-0.718, P = 0.002). CONCLUSIONS: There is an interaction between miR-23a and IRS-1 in the modulation of the migration and invasion of NSCLC cells. IRS-1 is variably expressed in NSCLC patients and correlates with NSCLC patient survival.
PURPOSE: To determine the interaction between insulin receptor substrate-1 (IRS-1) and miR-23a on the migration and invasion of non-small cell lung cancer (NSCLC) cells, and to examine IRS-1 expression in NSCLC tissues and its correlation with clinicopathologic characteristics. METHODS: The migration and invasion of A549 cells were measured using transwell assay. miR-23a levels were examined by quantitative reverse transcription-PCR and IRS-1 expression by Western blotting. The interaction between miR-23a and IRS-1 was examined by luciferase reporter assay. IRS-1 expression in 105 NSCLC specimens was determined by immunohistochemistry and its correlation with patient clinicopathologic characteristics was evaluated. RESULTS: Transwell assay revealed that miR-23a significantly promoted the migration and invasion of A549 cells with a 44.0 and 44.6 % increase in the number of migrated and invading cells, respectively. Luciferase assay showed that miR-23a markedly reduced luciferase activities of A549 cells co-transfected with plasmids overexpressing the 3' UTR of IRS-1 mRNA (P < 0.05). Co-transfection of A549 cells with miR-23a and plasmids overexpressing IRS-1 significantly reduced the increase in the number of migrated and invading cells mediated by miR-23a. Immunohistochemistry showed low IRS-1 expression in 26.7 % and high IRS-1 expression in 73.3 % of the NSCLC specimens. Kaplan-Meier analysis revealed that the overall survival and disease-free survival of NSCLC were markedly longer in patients with high IRS-1 expression than those with low IRS-1 expression (P = 0.002). Multivariate Cox regression analysis showed that IRS-1 was an independent prognostic factor for the overall survival of NSCLCpatients (RR 0.413 CI 0.238-0.718, P = 0.002). CONCLUSIONS: There is an interaction between miR-23a and IRS-1 in the modulation of the migration and invasion of NSCLC cells. IRS-1 is variably expressed in NSCLCpatients and correlates with NSCLCpatient survival.
Authors: Nozomu Yanaihara; Natasha Caplen; Elise Bowman; Masahiro Seike; Kensuke Kumamoto; Ming Yi; Robert M Stephens; Aikou Okamoto; Jun Yokota; Tadao Tanaka; George Adrian Calin; Chang-Gong Liu; Carlo M Croce; Curtis C Harris Journal: Cancer Cell Date: 2006-03 Impact factor: 31.743
Authors: Michael D Mattie; Christopher C Benz; Jessica Bowers; Kelly Sensinger; Linda Wong; Gary K Scott; Vita Fedele; David Ginzinger; Robert Getts; Chris Haqq Journal: Mol Cancer Date: 2006-06-19 Impact factor: 27.401