Screening miRNAs associated with resistance gemcitabine from exosomes in A549 lung cancer cells

Abstract

Ai-Ling Liang,1,2,3,* Shen-Lin Du,4,* Bin Zhang,1,2,3,* Jing Zhang,5 Xuan Ma,1–3 Cui-Yun Wu,5 Yong-Jun Liu1–31Medical Molecular Diagnostics Key Laboratory of Guangdong, Guangdong Medical University, Dongguan, Guangdong 523808, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, Guangdong 523808, People’s Republic of China; 3Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong 523808, People’s Republic of China; 4Department of Blood Transfusion, Dongguan Tung Wah Hospital, Dongguan, Guangdong 523210, People’s Republic of China; 5The Clinical Laboratory of Shunde Hospital, Southern Medical University, Shunde 528300, People’s Republic of China*These authors contributed equally to this workPurpose: To establish a gemcitabine-resistant lung adenocarcinoma cell line, A549/G+, and to screen the differences of miRNA expression in exosomes from A549 and A549/G+ cells.Methods: A549 cells were exposed in gemcitabine until they were resistant to gemcitabine, and extracted exosomes from A549 and A549/G+. The RNAs from exosomes were subjected to miRNA expression microarray experiments.Results: After 39 weeks of continuous induction, we induced drug resistance in A549 cells. The resistance index was 6. Via GeneChip miRNA 4.0 analysis, there were 446 differential miRNAs between A549 and A549/G+. Target gene prediction and pathway analysis discovered the microRNAs in the intersections may participate in drug resistance.Conclusion: These differential miRNAs help to do in-depth research to elucidate the mechanism of resistance to gemcitabine in non-small cell lung cancer.Keywords: non-small cell lung cancer, NSCLC, exosomes, miRNA, microarray, drug resistance, gemcitabine

Keywords

• Non-small cell lung cancer (NSCLC)
• exosomes
• miRNA
• microarray
• drug resistance
• gemcitabine