MicroRNA-375 confers cisplatin resistance by regulating KRAS expression in non-small cell lung cancer cell

Cisplatin is a classic chemotherapeutic drug that has been widely used for non small cell lung cancer (NSCLC) treatment, but NSCLC cells are often resistant to primary or acquired cisplatin therapy. Several studies have shown that miR-375 is significantly elevated in tumor and suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-375 significantly inhibited apoptosis, enhanced cell proliferation and increased the resistance of tumor cells to cisplatin in NSCLC H1975 cells. Furthermore, knock-down of miR-375 reversed these effects on H1975 cells and increased the sensitivity of H1975 to cisplatin chemotherapy. Finally, we showed that miR-375 targeted the KRAS gene, and directly regulated the expression of KRAS mRNA. These results demonstrate that miR-375 may play an important role in the cisplatin resistance of NSCLC.