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

Ai-Ling Liang; Shen-Lin Du; Bin Zhang; Jing Zhang; Xuan Ma; Cui-Yun Wu; Yong-Jun Liu

doi:10.2147/CMAR.S209149

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

Cancer Manag Res. 2019 Jul 8:11:6311-6321. doi: 10.2147/CMAR.S209149. eCollection 2019.

Authors

Ai-Ling Liang^#^{1

2

3}, Shen-Lin Du^#⁴, Bin Zhang^#^{1

2

3}, Jing Zhang⁵, Xuan Ma^{1

2

3}, Cui-Yun Wu⁵, Yong-Jun Liu^{1

2

3}

Affiliations

¹ Medical Molecular Diagnostics Key Laboratory of Guangdong, Guangdong Medical University, Dongguan, Guangdong 523808, People's Republic of China.
² Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, Guangdong 523808, People's Republic of China.
³ Department of Clinical Biochemistry, Guangdong Medical University, Dongguan, Guangdong 523808, People's Republic of China.
⁴ Department of Blood Transfusion, Dongguan Tung Wah Hospital, Dongguan, Guangdong 523210, People's Republic of China.
⁵ The Clinical Laboratory of Shunde Hospital, Southern Medical University, Shunde 528300, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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: NSCLC; drug resistance; exosomes; gemcitabine; miRNA; microarray; non-small cell lung cancer.