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Journal of Cancer Research and Clinical Oncology

Published in:

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

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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2014

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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Title: miR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells
Authors: Mengru Cao
Yulian Li
Hailing Lu
Qingwei Meng
Long Wang
Li Cai
Xiaoqun Dong
Publication date: 01-10-2014
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2014
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1725-0

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

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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