M i R -182-5p I nduced by HIF-1α Promotes Tumorigenesis and Metastasis via Targeting ZFP36L1 in Nasopharyngeal Carcinoma
Abstract Accumulating evidence indicates that dysregulation of human microRNAs could serve as diagnostic and prognostic biomarkers in nasopharyngeal carcinoma (NPC). In the present study, we found that up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36 ring finger protein like 1 (ZFP36L1) at two sites in its 3’ un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC primary tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). Taken together, our data suggest that miR-182-5p facilitates NPC development and progression through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.