MicroRNA-25-3p promotes cisplatin resistance in Non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT route

Abstract

ABSTRACT MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, p-AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC.