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01-12-2014 | Translational Research and Biomarkers

Suppression of Dicer Increases Sensitivity to Gefitinib in Human Lung Cancer Cells

Authors: Jui-Chieh Chen, PhD, Yen-Hao Su, MD, Ching-Feng Chiu, PhD, Yi-Wen Chang, PhD, Yang-Hao Yu, MD, PhD, Chi-Feng Tseng, MS, Hsin-An Chen, MD, PhD, Jen-Liang Su, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

Abstract

Background

Accumulating evidence is revealing an important role of microRNA (miRNA) in tumor progression and chemotherapeutic resistance. Dicer is a cytoplasmic endoribonuclease type III crucial for production of mature miRNAs. The aberrant expression of Dicer has also been reportedly associated with clinical aggressiveness, prognosis, and patient survival in various cancer types. However, the molecular mechanisms of Dicer in acquired gefitinib resistance are still not clear.

Methods

In this study, we analyzed the protein level of Dicer between gefitinib-sensitive (PC9) and gefitinib-resistant (PC9/GR) non-small-cell lung cancer (NSCLC) cell lines by Western blot analysis. Silence and overexpression of the Dicer were performed to investigate the effects on gefitinib sensitivity, as assessed by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and sub-G1 assay of flow cytometry. To further explore the mechanism of chemoresistance, we examined whether Dicer knockdown led to modulating specific miRNAs and its miRNA target genes.

Results

Dicer expression was significantly increased in PC9/GR compared with PC9 cells. Knockdown of Dicer restores gefitinib sensitivity in resistant cells, and overexpression of Dicer enhances resistance to gefitinib in sensitive cells. Silencing of Dicer induces sensitivity to gefitinib in NSCLC cells through the downregulation of miR-30b/c and miR-221/222 to increase the protein level of caspase-3, resulting in an increase in gefitinib-induced apoptosis.

Conclusions

Dicer contributes to the resistance to gefitinib in lung cancer. These results indicate that Dicer may be a target for diagnosis and therapy of patients with resistance to gefitinib.

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Title: Suppression of Dicer Increases Sensitivity to Gefitinib in Human Lung Cancer Cells
Authors: Jui-Chieh Chen, PhD
Yen-Hao Su, MD
Ching-Feng Chiu, PhD
Yi-Wen Chang, PhD
Yang-Hao Yu, MD, PhD
Chi-Feng Tseng, MS
Hsin-An Chen, MD, PhD
Jen-Liang Su, PhD
Publication date: 01-12-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-014-3673-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Suppression of Dicer Increases Sensitivity to Gefitinib in Human Lung Cancer Cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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