title: Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth.
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.
authors.affiliation: a Department of Pharmacology and Toxicology , German University in Cairo, Main Entrance Al Tagamoa Al Khames , Cairo , Egypt .
authors.forename: Injie Omar
authors.initials: IO
authors.lastname: Fawzy
authors.affiliation: b Department of Clinical Pathology , Ain Shams University , Khalifa El-Maamoun St, Abbasiya Square , Cairo , Egypt .
authors.forename: Mohammed Tarif
authors.initials: MT
authors.lastname: Hamza
authors.affiliation: c Department of Endemic Medicine and Hepatology , Cairo University , Kasr El-Aini St , Cairo , Egypt , and.
authors.forename: Karim Adel
authors.initials: KA
authors.lastname: Hosny
authors.affiliation: c Department of Endemic Medicine and Hepatology , Cairo University , Kasr El-Aini St , Cairo , Egypt , and.
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.affiliation: d Department of Biology , American University in Cairo , AUC Avenue , New Cairo City, Cairo , Egypt.
authors.forename: Ahmed Ihab
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C000597236:IGF1R protein, human; C406144:IGF2BP1 protein, human; C498779:IGF2BP2 protein, human; C498780:IGF2BP3 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D017451:Receptors, Somatomedin; C487931:mirnlet7 microRNA, human; D017526:Receptor, IGF Type 1
keywords: Insulin-like growth factor 1 receptor; hepatocellular carcinoma; insulin-like growth factor-2-mRNA-binding protein; let-7i; microRNA; post-transcriptional regulation