Lung Cancer: Lung Cancer II |

Microrna-144 Expression Overcomes Resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR Mutant Lung Cancer Cells by Targeting Survivin FREE TO VIEW

Ki Eun Hwang, MD; Eun-Taik Jeong, MD; Hak-Ryul Kim, MD
Author and Funding Information

Wonkwang University Hospital, Iksan city, Korea (the Republic of)

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):714A. doi:10.1016/j.chest.2016.08.809
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM

PURPOSE: The emergence of drug resistance in cancer patients limits the success rate of clinical chemotherapy. MicroRNAs may play a role in chemoresistance and may be involved in modulating some drug resistance-related pathways in cancer cells. In this study, we hypothesized that microRNA-survivin interaction was involved in resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) cells. We focused on the effect of altered expression of microRNAs on EGFR-TKI resistance in EGFR-TKI-resistant cell lines.

METHODS: We performed a microarray analysis to identify microRNAs whose expression level was altered in EGFR-TKI-resistant cells. We confirmed the altered expression of miR144-3p, which was predicted to target survivin, in EGFR-TKI-resistant cells by quantitative real-time PCR, using the HCC827, HCC827GR, and H1975 NSCLC cell lines.

RESULTS: Expression of miR144-3p in EGFR-TKI-resistant cell lines reversed EGFR-TKI chemoresistance through enhancing apoptosis by modulating survivin expression. Luciferase reporters containing the 3′ untranslated region of survivin mRNA were used to demonstrate that miR144-3p could directly target survivin. We observed an inverse correlation between the expression levels of miR144-3p and survivin mRNA.

CONCLUSIONS: Targeting the miR144-3p/survivin interaction is a potential strategy for reversing chemoresistance in NSCLC.

CLINICAL IMPLICATIONS: This study suggested that miR144-3p regulates the acquired resistance to gefitinib in cell lines with mutations in EGFR by targeting survivin.

DISCLOSURE: The following authors have nothing to disclose: Ki Eun Hwang, Eun-Taik Jeong, Hak-Ryul Kim

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