This study aimed to identify a single miRNA or miR (microRNA) which regulates the three insulin‐like growth factor‐2‐mRNA‐binding proteins (IGF2BP1, 2 and 3). Bioinformatics predicted miR‐1275 to simultaneously target the three IGF2BPs, and screening revealed miR‐1275 to be underexpressed in hepatocellular carcinoma (HCC) tissues. Transfection of HuH‐7 cells with miR‐1275 suppressed IGF2BPs expression and all three IGF2BPs were confirmed as targets of miR‐1275. Ectopic expression of miR‐1275 and knockdown of IGF2BPs inhibited malignant cell behaviors, and also reduced IGF1R protein and mRNA. Finally IGF1R was validated as a direct target of miR‐1275. These findings indicate that the tumor‐suppressor miR‐1275 can control HCC tumor growth partially through simultaneously regulating the oncogenic IGF2BPs and IGF1R.
IGF2BP 1, 2 and 3 control the fate of many transcripts. Immunoprecipitation studies demonstrated the IGF2BPs to bind to IGF1R mRNA, and our laboratory has recently shown them to post-transcriptionally regulate IGF1R. This study sought to identify a microRNA regulating the IGF2BPs and consequently IGF1R. All three IGF2BPs were among the top-ranked predicted targets of let-7i. Let-7i was downregulated in HCC tissues, and transfection of HuH-7 with let-7i inhibited malignant cell behaviors and decreased IGF2BPs transcripts. Direct binding of let-7i to IGF2BP2 and IGF2BP3 3'UTRs was confirmed, and the effect of let-7i caused a decrease in the IGF2BPs' target gene, the IGF1R. IGF1R mRNA was inversely correlated with let-7i in HCC tissues and was reduced upon let-7i transfection into HuH-7. Reporter assays validated IGF1R as a target of let-7i. Therefore, let-7i may control HCC tumorigenesis by regulating IGF1R directly and indirectly by interrupting the interplay between IGF1R and the IGF2BPs.
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