title: miR-15a enhances the anticancer effects of cisplatin in the resistant non-small cell lung cancer cells.
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.
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey. vildanbcetintas@gmail.com.
authors: Vildan
authors: V
authors: Bozok Çetintaş
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Aslı
authors: A
authors: Tetik Vardarlı
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Zekeriya
authors: Z
authors: Düzgün
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Burçin
authors: B
authors: Tezcanlı Kaymaz
authors: Department of Embryology and Histology, Ege University School of Medicine, Izmir, Turkey.
authors: Eda
authors: E
authors: Açıkgöz
authors: Department of Embryology and Histology, Ege University School of Medicine, Izmir, Turkey.
authors: Hüseyin
authors: H
authors: Aktuğ
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Buket
authors: B
authors: Kosova Can
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Cumhur
authors: C
authors: Gündüz
authors: Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
authors: Zuhal
authors: Z
authors: Eroğlu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: Apoptosis; Autophagy; Cisplatin resistance; Non-small cell lung cancer; hsa-miR-15a-3p