Down‐regulation of miR‐26b induces cisplatin resistance in nasopharyngeal carcinoma by repressing JAG1

Abstract

Therapy against nasopharyngeal carcinoma (NPC) is hurdled by chemoresistance. Recent studies found that microRNA (miRNA) are important regulators of cancer resistance. In this study, we aimed to explore the role and mechanism of miR‐26b in regulating NPC cisplatin (CDDP) resistance. Real‐time PCR was used to evaluate miR‐26b levels in CDDP‐resistant and CDDP‐sensitive NPC cells, as well as human NPC tissues. MiR‐26b was ectopically overexpressed in CDDP‐resistant cells, followed by monitoring changes in cell viability and apoptosis. Interaction between JAG1 and miR‐26b was characterized by dual‐luciferase reporter assay. Furthermore, we investigated whether ectopic JAG1 expression reversed CDDP sensitivity induced by miR‐26b overexpression. The effect of FOXD3 down‐regulation on miR‐26b was also evaluated. Our results indicate that miR‐26b was lower in the CDDP‐resistant NPC cells, human NPC tissue, particularly in secondary metastases. Ectopic expression of miR‐26b sensitized NPC cells to CDDP. JAG1 is a target of miR‐26b, and its expression is inversely correlated with miR‐26b. Overexpression of JAG1 reversed the CDDP sensitivity induced by miR‐26b overexpression. FOXD3 expression was also down‐regulated in CDDP‐resistant NPC. FOXD3 promoted miR‐26b expression and down‐regulation of FOXD3 suppressed miR‐26b expression. Down‐regulation of miR‐26b is closely correlated with the CDDP resistance in NPC.

Keywords

• cisplatin resistance
• FOXD3
• JAG1
• miR‐26b
• nasopharyngeal carcinoma