Open AccessDown‐regulation of miR‐26b induces cisplatin resistance in nasopharyngeal carcinoma by repressing JAG 1
Author(s) -
Shi Lei,
Yin Wei,
Zhang Zhiyu,
Shi Guanggang
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12135
Subject(s) - nasopharyngeal carcinoma , ectopic expression , cisplatin , apoptosis , cancer research , microrna , chemistry , luciferase , biology , microbiology and biotechnology , cell culture , transfection , gene , medicine , chemotherapy , biochemistry , genetics , radiation therapy
Therapy against nasopharyngeal carcinoma ( NPC ) is hurdled by chemoresistance. Recent studies found that micro RNA (mi RNA ) 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 JAG 1 and miR‐26b was characterized by dual‐luciferase reporter assay. Furthermore, we investigated whether ectopic JAG 1 expression reversed CDDP sensitivity induced by miR‐26b overexpression. The effect of FOXD 3 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 . JAG 1 is a target of miR‐26b, and its expression is inversely correlated with miR‐26b. Overexpression of JAG 1 reversed the CDDP sensitivity induced by miR‐26b overexpression. FOXD 3 expression was also down‐regulated in CDDP ‐resistant NPC . FOXD 3 promoted miR‐26b expression and down‐regulation of FOXD 3 suppressed miR‐26b expression. Down‐regulation of miR‐26b is closely correlated with the CDDP resistance in NPC .