miR-29c regulates resistance to paclitaxel in nasopharyngeal cancer by targeting ITGB1.

ABSTRACT

Paclitaxel (Taxol) is an anticancer taxane drug commonly used in the treatment of nasopharyngeal carcinoma (NPC). However, resistance to paclitaxel is a major difficulty in developing an effective therapy against NPC. MicroRNAs (miRNAs) are known to regulate genes that are involved in drug resistance. We assessed the effects of miR-29c, an miRNA identified in a genome-wide study of Taxol resistance, on genes associated with resistance in NPC cells. We established Taxol resistance in two human NPC cell lines, SUNE-1 and C666-1 (SUNE-1-Taxol and C666-1-Taxol) and found that miR-29c was downregulated and integrin beta-1 (ITGB1) was upregulated in Taxol-resistant NPC cells compared with parental NPC cells. Further investigations using a TUNEL assay and BAX/BCL-2 ratio, found that overexpression of miR-29c and knockdown of ITGB1 can resensitize drug-resistant NPC cells to Taxol and promote apoptosis. In addition, a dual-luciferase reporter assay indicated that ITGB1 is the target of miR-29c. Furthermore, silencing miR-29c markedly increased Taxol-resistant NPC tumor growth in a nude mouse xenograft model while knockdown of ITGB1 reversed this result. Overall, these data demonstrate that miR-29c regulates resistance to Taxol in NPC by targeting ITGB1. Our research indicates that miR-29c may have potential use in Taxol-resistant NPC therapy.