Abrogating the interplay between IGF2BP1, 2 and 3 and IGF1R by let-7i arrests hepatocellular carcinoma growth

Area of Science:

• Molecular Biology
• Oncology
• Gene Regulation

Background:

• Insulin-like Growth Factor 2 Binding Proteins (IGF2BPs) 1, 2, and 3 are crucial regulators of transcript fate.
• IGF2BPs have been shown to bind and post-transcriptionally regulate Insulin-like Growth Factor 1 Receptor (IGF1R) mRNA.
• The role of microRNAs in regulating IGF2BPs and their impact on IGF1R in hepatocellular carcinoma (HCC) remains to be fully elucidated.

Purpose of the Study:

• To identify a specific microRNA that regulates IGF2BPs and, consequently, IGF1R.
• To investigate the role of let-7i in hepatocellular carcinoma (HCC) progression.
• To determine the regulatory relationship between let-7i, IGF2BPs, and IGF1R in HCC.

Main Methods:

• Bioinformatic prediction identified let-7i as a potential regulator of all three IGF2BPs.
• let-7i mimic transfection into HuH-7 cells (a HCC cell line).
• Quantitative analysis of IGF2BP and IGF1R transcripts, 3'UTR reporter assays, and correlation analysis in HCC tissues.

Main Results:

• let-7i was found to be downregulated in HCC tissues.
• Transfection with let-7i inhibited malignant cell behaviors and decreased IGF2BP transcripts in HuH-7 cells.
• Direct binding of let-7i to IGF2BP2 and IGF2BP3 3'UTRs was confirmed, leading to decreased IGF1R expression. IGF1R mRNA inversely correlated with let-7i in HCC tissues.

Conclusions:

• let-7i directly targets IGF2BP2 and IGF2BP3, reducing their levels.
• let-7i regulates IGF1R expression both directly and indirectly by modulating the IGF2BP-IGF1R axis.
• let-7i acts as a tumor suppressor in HCC, potentially controlling tumorigenesis through the regulation of IGF1R and IGF2BPs.