MiR-146a-5p Level in Serum Exosomes Predicts Therapeutic Effect of Cisplatin in Non-small Cell Lung Cancer

Objective: Lung cancer is the most common cause of death in cancer worldwide, and cisplatin plays an important role in its treatment. However, the response to chemotherapy is poorly attributable to drug resistance. Our present study aimed to investigate the relation of the exosomal miR-146a-5p level with the chemosensitivity of NSCLC to cisplatin and the molecular mechanism that miR-146a-5p mediated to effect on chemotherapy response.

Patients And Methods: The exosomes were isolated by ExoQuick kit. The exosomal morphology and particle size distribution were evaluated by the transmission electron microscopy and nanoSight assay respectively. Cell proliferation was detected using the MTT assay. NSCLC cells were infected with mimics or inhibitor to overexpress or downregulate miR-146a level. Besides, Quantitative real-time PCR, Western blot analysis, and immunohistochemistry were applied to detect the relative miRNA and protein levels.

Results: Advanced NSCLC patients with low serum exosomal miR-146a-5p levels had higher recurrence rates than those with high levels. A549/DDP cells and exosomes expressed higher miR-146a-5p than A549. In the process of cisplatin-induced drug resistance, the expression of miR-146a-5p decreased in either NSCLC cell lines or the exosomes gradually. What's more, the overexpression of miR-146a-5p could reverse the resistance of A549/DDP. And the possible mechanism of miR-146a-5p increasing chemosensitivity of NSCLC to cisplatin could be targeting Atg12 to inhibit autophagy.

Conclusions: Serum exosomal miR-146a-5p may be a new biomarker predicting the efficacy of cisplatin for NSCLC patients and real-time monitoring drug resistance.