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Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 5, pp 973–984 | Cite as

miR-181c contributes to cisplatin resistance in non-small cell lung cancer cells by targeting Wnt inhibition factor 1

  • Haifeng Zhang
  • Baoli Hu
  • Zuopei Wang
  • Feng Zhang
  • Haitao Wei
  • Li Li
Original Article

Abstract

Purpose

miRNAs are implicated in drug resistance of multiple cancers including non-small cell lung cancer (NSCLC), highlighting the potential of miRNAs as chemoresistance regulators in cancer treatment. This study aims to explore the relationship between miR-181c and chemoresistance of NSCLC cells.

Methods

qRT-PCR was conducted to examine the expression of miR-181c in NSCLC tissues, and parental and cisplatin (DDP)-resistant NSCLC cells. MTT assay and flow cytometry were performed to detect the survival rate and apoptosis in NSCLC cells. Luciferase reporter assay was performed to confirm the potential target of miR-181c. Xenograft tumor experiment was applied to confirm the effect of miR-181c on DDP sensitivity of DDP-resistant NSCLC cells in vivo.

Results

miR-181c was upregulated in NSCLC tissues, and parental and DDP-resistant NSCLC cells. miR-181c downregulation or WIF1 overexpression increased DDP sensitivity of DDP-resistant NSCLC cells by decreasing survival rate and promoting DDP-induced apoptosis. miR-181c was demonstrated to be able to bind to WIF1 and negatively regulate the expression of WIF1. WIF1 knockdown abolished anti-miR-181c-induced DDP sensitivity. Moreover, anti-miR-181c suppressed the Wnt/β-catenin pathway by regulating WIF1. XAV939 treatment reversed miR-181c-induced increase in IC50 value and miR-181c-triggered decrease in apoptosis. Finally, anti-miR-181c improved DDP sensitivity of DDP-resistant NSCLC cells in vivo.

Conclusion

miR-181c contributed to DDP resistance in NSCLC cells through activation of the Wnt/β-catenin pathway by targeting WIF1, providing a potential therapeutic application for the treatment of patients with DDP-resistant NSCLC in the future.

Keywords

MiR-181c DDP resistance NSCLC WIF1 Wnt/β-catenin pathway 

Abbreviations

NSCLC

Non-small cell lung cancer

DMSO

Dimethyl sulfoxide

OD

Optical density

miRNAs

MicroRNAs

SDS–PAGE

Odium dodecyl sulfate polyacrylamide gel electrophoresis

HRP

Horseradish peroxidase

SPF

Specific pathogen-free

SD

Standard deviation

Notes

Acknowledgements

This work was supported by Science and Technology Project of Henan Province (172102310158).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Cardiothoracic SurgeryHuaihe Hospital of Henan UniversityKaifengChina
  2. 2.School of NursingHenan UniversityKaifengChina

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