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

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

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.

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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

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Acknowledgements

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

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Author notes

  1. Haifeng Zhang and Baoli Hu have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Haifeng Zhang, Baoli Hu, Zuopei Wang, Feng Zhang & Haitao Wei

  2. School of Nursing, Henan University, Jinming Campus, Kaifeng, 475000, China

    Li Li

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  1. Haifeng Zhang
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Correspondence to Li Li.

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Zhang, H., Hu, B., Wang, Z. et al. miR-181c contributes to cisplatin resistance in non-small cell lung cancer cells by targeting Wnt inhibition factor 1. Cancer Chemother Pharmacol 80, 973–984 (2017). https://doi.org/10.1007/s00280-017-3435-1

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