MicroRNA-1249 targets four-jointed box kinase 1 and reduces cell proliferation, migration and invasion of colon adenocarcinoma.

Abstract

MiR-1249 was demonstrated to be dysregulated and related to prognosis in cancers. It has been reported to be significantly down-regulated in colon adenocarcinoma (COAD). The present study aimed to explore the clinical value and biological roles of miR-1249 in the progression of COAD. miRWalk was applied to predict potential targets of miR-1249. We investigated the expression patterns of miR-1249 and its potential target Four-Jointed Box Kinase 1 (FJX1) in COAD samples from The Cancer Genome Atlas (TCGA) or ONCOMINE database. Kaplan-Meier with a log-rank test was used to reveal the relationship between overall survival (OS) and miR-1249/FJX1. The predictive ability of miR-1249/FJX1 was investigated using univariate and multivariate Cox regression models. CCK-8 and Transwell assays were performed to determine whether miR-1249 was connected with cell viability, migration and invasion. A luciferase reporter assay was applied to verify the association of miR-1249 and FJX1 as its predicted target gene. We predicted and confirmed FJX1 to be a target gene of miR-1249. MiR-1249 was down-regulated in COAD samples and cell lines. Univariate and multivariate analysis showed that the expression of FJX1 could be regarded as independent predictor for COAD. Moreover, miR-1249 and FJX1 were respectively the indicators of favorable and poor OS. MiR-1249 over-expression repressed cell growth, migration and invasion. Overexpression of FJX1 in cells treated with miR-1249 mimic abolished the inhibitory effect of miR-1249 on cell growth, migration and invasion. miR-1249 exerts a suppressive effect on cell proliferation, migration and invasion in COAD, which is possibly achieved via modulating FJX1.