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01-02-2016 | Original Article

miR-15a enhances the anticancer effects of cisplatin in the resistant non-small cell lung cancer cells

Authors: Vildan Bozok Çetintaş, Aslı Tetik Vardarlı, Zekeriya Düzgün, Burçin Tezcanlı Kaymaz, Eda Açıkgöz, Hüseyin Aktuğ, Buket Kosova Can, Cumhur Gündüz, Zuhal Eroğlu

Published in: Tumor Biology | Issue 2/2016

Abstract

Platinum-based chemotherapies have long been used as a standard treatment in non-small cell lung cancer. However, cisplatin resistance is a major problem that restricts the use of cisplatin. Deregulated cell death mechanisms including apoptosis and autophagy could be responsible for the development of cisplatin resistance and miRNAs are the key regulators of these mechanisms. We aimed to analyse the effects of selected miRNAs in the development of cisplatin resistance and found that hsa-miR-15a-3p was one of the most significantly downregulated miRNAs conferring resistance to cisplatin in Calu1 epidermoid lung carcinoma cells. Only hsa-miR-15a-3p mimic transfection did not affect cell proliferation or cell death, though decreased cell viability was found when combined with cisplatin. We found that induced expression of hsa-miR-15a-3p via mimic transfection sensitised cisplatin-resistant cells to apoptosis and autophagy. Our results demonstrated that the apoptosis- and autophagy-inducing effects of hsa-miR-15a-3p might be due to suppression of BCL2, which exhibits a major connection with cell death mechanisms. This study provides new insights into the mechanism of cisplatin resistance due to silencing of the tumour suppressor hsa-miR-15a-3p and its possible contribution to apoptosis, autophagy and cisplatin resistance, which are the devil’s triangle in determining cancer cell fate.

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Title: miR-15a enhances the anticancer effects of cisplatin in the resistant non-small cell lung cancer cells
Authors: Vildan Bozok Çetintaş
Aslı Tetik Vardarlı
Zekeriya Düzgün
Burçin Tezcanlı Kaymaz
Eda Açıkgöz
Hüseyin Aktuğ
Buket Kosova Can
Cumhur Gündüz
Zuhal Eroğlu
Publication date: 01-02-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3950-9

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