Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth |
| |
| Authors: | Injie Omar Fawzy Mohammed Tarif Hamza Karim Adel Hosny Gamal Esmat |
| |
| Affiliation: | 1. Department of Pharmacology and Toxicology, German University in Cairo, Main Entrance Al Tagamoa Al Khames, Cairo, Egypt,;2. Department of Clinical Pathology, Ain Shams University, Khalifa El-Maamoun St, Abbasiya Square, Cairo, Egypt,;3. Department of Endemic Medicine and Hepatology, Cairo University, Kasr El-Aini St, Cairo, Egypt, and |
| |
| 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. |
| |
| Keywords: | Insulin-like growth factor 1 receptor insulin-like growth factor-2-mRNA-binding protein microRNA let-7i hepatocellular carcinoma post-transcriptional regulation |
|
|
