Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth. (2nd January 2016)

• Record Type: Journal Article
• Authors: Fawzy, Injie Omar; Hamza, Mohammed Tarif; Hosny, Karim Adel; Esmat, Gamal; Abdelaziz, Ahmed Ihab
• Is Part Of: Growth factors. Volume 34:Number 1/2(2016:Feb.)
• Page Start: 42
• Page End: 50
• Publication Date: 2016-01-02
• Subjects: Insulin-like growth factor 1 receptor -- insulin-like growth factor-2-mRNA-binding protein -- microRNA -- let-7i -- hepatocellular carcinoma -- post-transcriptional regulation; Growth factors -- Periodicals; Physiology -- Periodicals; 611
• DOI: 10.3109/08977194.2016.1169532
• Languages: English
• ISSNs: 0897-7194

Abstract

Abstract: 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.