miR-1275: A single microRNA that targets the three IGF2-mRNA-binding proteins hindering tumor growth in hepatocellular carcinoma

•miR-1275 is markedly underexpressed in HCC and cirrhotic liver tissue.•miR-1275 reduces IGF2BP1, 2, and 3 mRNA, and directly binds to their 3′UTRs.•miR-1275 is a tumor suppressor, reducing several tumorigenic properties of HuH-7.•miR-1275 mimics and IGF2BP siRNAs significantly reduce IGF1R protein and mRNA.•IGF1R is also directly targeted by miR-1275. 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.