Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth
2016; Taylor & Francis; Volume: 34; Issue: 1-2 Linguagem: Inglês
10.3109/08977194.2016.1169532
ISSN1029-2292
AutoresInjie Omar Fawzy, Mohammed Tarif Hamza, Karim Adel Hosny, Gamal Esmat, Ahmed Ihab Abdelaziz,
Tópico(s)Cancer-related molecular mechanisms research
ResumoAbstractIGF2BP 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.KeywordsInsulin-like growth factor 1 receptorinsulin-like growth factor-2-mRNA-binding proteinmicroRNAlet-7ihepatocellular carcinomapost-transcriptional regulation Declaration of interestThe study was funded by the Egyptian Science and Technology Development Fund (STDF) [grant number 4242]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors report no declarations of interest.
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