Abstract

Exosomes were reported to transport bioactive molecules and influence the biology behavior of recipient cells. In order to study the role of exosomal microRNAs in the mechanism of cisplatin resistance to lung cancer cells, we analyzed the expression profiles of microRNAs in A549, A549/DDP cells and their exosomes by microarray. The results showed that a certain proportion of microRNAs were co-expressed in the cells and exosomes. Linear regression analysis showed that the expression of microRNAs in A549 and A549/DDP cells were strongly correlated with those in their respective exosomes. The expression level of 5 microRNAs (miR-197-5p, miR-4443, miR-642a-3p, miR-27b-3p and miR-100-5p) with the most differential expression were verified by qRT-PCR. The results were consistent with those of the microarray. Target gene prediction and pathway analysis discovered that the microRNAs in the intersections may participate in drug resistance. And the prediction of their association with diseases found that most of these microRNAs was associated with lung cancer. We could draw a preliminary conclusion that microRNAs in exosomes may be involved in the drug resistance of lung cancer cells to cisplatin.

Highlights

  • Lung cancer is one of malignant tumors which can maximally threaten the population’s health and life worldwide

  • Results showed that the inhibitory concentration to produce 50% cell death (IC50) values of DDP were 1.93±0.53 μg/ml and 21.15±1.07 μg/ml for A549 and A549/DDP, respectively

  • The resistance index is more than 10 folds, which indicates that A549/DDP cells are resistant to DDP

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Summary

Introduction

Lung cancer is one of malignant tumors which can maximally threaten the population’s health and life worldwide. Recent studies [2, 3] indicated that there are a large number of vesicles of which the diameters are varying from 30nm~100nm in body fluid. These vesicles are encapsulated by the lipid bilayer. Exosomes are involved in tumor occurrence, development, invasion, metastasis, immunosuppression, drug resistance and can be applied in clinical diagnosis and treatment [11, 12]. Studies showed that the treatment of tumor can be achieved through exosomes [13]. Exosomes can act as drug carrier, so as to achieve the therapeutic effect through carrying miRNA into the target cells and aiming to specific target genes [14]

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