MicroRNA-429 overexpression overcomes imatinib resistance of glioma cells by negatively regulating lysophosphatidic acid receptor 1

Glioma is one of the most aggressive and lethal malignancies in central nervous system. It has been reported that miR-429 is declined in glioma and functions as a tumor suppressor. Nonetheless, the potential role of miR-429 in drug resistance of glioma is still ambiguous. Stable imatinib-resistant lines U251-AR and T98G-AR were established using glioma cell lines U251 and T98G. Cell apoptosis and cycle were analyzed by flow cytometry, and CCK-8 assay was utilized to measure cell viability. Protein and RNA levels were tested with western blot and RT-qPCR. The predicted binding site was confirmed by dual luciferase reporter assay. Imatinib-resistant U251-AR and T98G-AR cells presented lower level of miR-429 and higher level of LPAR1. MiR-429 overexpression obviously promoted imatinib sensitivity in glioma cells, indicated by the reduced IC50 value, facilitated cell apoptosis and cell cycle arrest at G0/G1 phase, and downregulated multidrug resistance-related proteins. LPAR1 was verified as a direct target of miR-429 and its expression was negatively regulated by miR-429. Additionally, overexpression of LPAR1 restrained the biological function of miR-429 on imatinib chemoresistance. MiR-429 partly sensitized glioma cells to imatinib via downregulation LPAR1, which might provide an approach to overcome imatinib chemoresistance during glioma treatment. Imatinib-resistant U251-AR and T98G-AR cells display lower level of miR-429.Re-expression of miR-429 significantly sensitizes glioma cells to imatinib.LPAR1 is a direct target of miR-429.LPAR1 represses the biological effects of miR-429 on imatinib chemoresistance. Imatinib-resistant U251-AR and T98G-AR cells display lower level of miR-429. Re-expression of miR-429 significantly sensitizes glioma cells to imatinib. LPAR1 is a direct target of miR-429. LPAR1 represses the biological effects of miR-429 on imatinib chemoresistance.