Exosome-Reversed Chemoresistance to Cisplatin in Non-Small Lung Cancer Through Transferring miR-613

Introduction: Non-small lung Cancer (NSCLC) is one of the most common malignant tumors in the world. Chemoresistance is the main reason of adverse effects leading to the death of patients; thus, it is important to discover the potential target of chemotherapeutic resistance.

Methods: The expression of differentially expressed miRNA was detected in BEAS-2B, A549 and A549/cisplatin (DDP) by qRT-PCR. Transmission electron microscopy (TEM) and exosome biomarkers were used to validate the extracted exosome. Cells incubated with miR-613 enriched exosomes were used to detect the function of exo-miR-613 in vitro. Then, exo-miR-613 was injected to mice treated with DDP to investigate the function role of exo-miR-613 in vivo.

Results: Comparing to BEAS-2B, the expression of miR-613 inA549 was significantly reduced, which was more obvious in A549/DDP. After incubated with exo-miR-613 and corresponding exo-negative control (NC), we found overexpression of miR-613 remarkably increased the inhibition of cell proliferation induced by cisplatin. Exo-miR-613 fused into cells to significantly enhance the inhibited effect of DDP on the proliferation, migration and showed a promotion on cell Apoptosis and DNA damage. The in vivo study showed that exo-miR-613 significantly inhibited the tumor growth, and promote the sensitivity to DDP, probably by down-regulating the expressions of GJA1, TBP and EIF-4E in tumor cells and tissues.

Conclusion: Exo-miR-613 reversed chemoresistance to DDP in NSCLC cell to involve in the process of tumor progression, and might be a potential therapeutic strategy for NSCLC.