MiR-30a sensitized lung cancer against neoadjuvant chemotherapy by depressing autophagy

Abstract

Objective: This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way.

Methods: We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting.

Results: Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P < 0.05). Moreover, DDP combined with PEM attenuated viability and proliferation, but, on the contrary, promoted autophagy of H1299 and H460 cell lines (P < 0.05). However, miR-30a undermined resistance of NSCLC cells against DDP and PEM (P < 0.05), and it suppressed DDP/PEM-induced autophagy and promoted DDP/PEM-triggered apoptosis of NSCLC cells (P < 0.05).

Conclusions: Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.

Keywords: NSCLC; autophagy; cisplatin; miR-30a; neoadjuvant chemotherapy; pemetrexed; sensitivity.