MicroRNA-615-5p targets insulin-like growth factor 2 and exerts tumor-suppressing functions in human esophageal squamous cell carcinoma.

ABSTRACT

To investigate the expression pattern, clinical significance and functional roles of microRNA (miR)-615-5p in human esophageal squamous cell carcinoma (ESCC), , quantitative real-time PCR was performed to detect expression levels of miR­615­5p in ESCC tissues and cell lines. Associations between miR­615­5p expression and various clinicopathological features of ESCC patients were also statistically evaluated. The candidate targets of miR­615­5p were identified by integrating bioinformatics miRNA target prediction, western blot analysis and luciferase reporter assay. Moreover, the functions of miR­615­5p in ESCC cell migration and invasion were determined using the transfection of miRNA mimics, or co-transfected with miRNA mimics and the expression vector of its target gene. As a result, miR­615­5p expression in ESCC tissues and cells were markedly lower than those in non-cancerous esophageal mucosa and human normal esophageal cells, respectively (both P<0.001). miR­615­5p downregulation was significantly associated with advanced tumor-node-metastasis stage, positive lymph node metastasis and moderate-poor differentiation. Functionally, the re-expression of miR­615­5p suppressed the invasion and migration of ESCC cells in vitro. Interestingly, insulin-like growth factor 2 (IGF2) was identified as a direct target gene of miR­615­5p, and the inhibitory effects of miR­615­5p in ESCC cell motility were reversed by the restoration of IGF2 expression. In conclusion, miR­615­5p downregulation may be an underlying molecular mechanism of development and progression of ESCC, and may function as a potential therapeutic target of this malignancy. Also, we illustrate that the miR­615­5p/IGF2 axis may bring important contributions to cell motility of human ESCC.