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MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

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Tumor Biology

Abstract

Patients with cervical cancer show minimal clinical response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). The molecular mechanisms underlying sensitivity to gefitinib are unknown. The purpose of this study was to investigate the possible mechanism by which microRNA-221 (miR-221) affects sensitivity to gefitinib. We showed that miR-221 expression was significantly increased in cervical cancer tissues compared with adjacent normal tissues. Upregulation of miR-221 expression in cervical cancer cells decreased PTEN expression levels, resulting in increased pAkt and BCL-2 expression. Importantly, gefitinib sensitivity was decreased by the upregulation of miR-221, which was blocked by pcDNA-PTEN co-transfection or by the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. These data suggest that miR-221 can reduce the sensitivity of cervical cancer cells to gefitinib through the PTEN/PI3K/Akt signaling pathway. miR-221 represents a potential target to increase the sensitivity to gefitinib in cervical cancer treatment.

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Abbreviations

NCCN:

National Comprehensive Cancer Network

TKIs:

Tyrosine kinase inhibitors

NSCLC:

Non-small-cell lung cancers

EGFR:

Epidermal growth factor receptor

miRNAs:

MicroRNAs

PTEN:

Phosphatase and tensin homolog deleted on chromosome ten

PI3K:

Phosphatidylinositol-3 kinase

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

MMP-2:

Matrix metalloproteinase 2

MAPK:

Mitogen-activated protein kinase

MET:

Hepatocyte growth factor

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Acknowledgments

This work was supported by a foundation of the Heilongjiang Provincial Educational Department, China (Grant No. 11551163).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China

    Juan Du, LiNa Wang, ChenXi Li, HuiLun Yang, YuanBo Li, Haiyang Hu, Hui Li & ZongFeng Zhang

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  1. Juan Du
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Correspondence to ZongFeng Zhang.

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Du, J., Wang, L., Li, C. et al. MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway. Tumor Biol. 37, 3939–3947 (2016). https://doi.org/10.1007/s13277-015-4247-8

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  • DOI: https://doi.org/10.1007/s13277-015-4247-8

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