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Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2014

01.10.2014 | Original Article – Cancer Research

miR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells

verfasst von: Mengru Cao, Yulian Li, Hailing Lu, Qingwei Meng, Long Wang, Li Cai, Xiaoqun Dong

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2014

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Abstract

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.
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Metadaten
Titel
miR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells
verfasst von
Mengru Cao
Yulian Li
Hailing Lu
Qingwei Meng
Long Wang
Li Cai
Xiaoqun Dong
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2014
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1725-0

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