MicroRNA Let-7b-5p Targets IGF1R to Inhibit the Progression of Hepatocellular Carcinoma Through the AKT/mTOR Pathway

Abstract

Background: Hepatocellular carcinoma (HCC) remains a major global health burden, with microRNA Let-7b-5p (Let-7b-5p) emerging as a potential tumor suppressor. However, its precise role and molecular mechanisms in HCC progression remain unclear, necessitating further investigation. Methods: We assessed Let-7b-5p expression in HCC versus normal hepatocytes via qRT-PCR and employed functional assays (clone formation, EdU, scratch, Transwell, apoptosis) to examine its effects on proliferation, migration, and cell death. Mechanistic studies combined bioinformatics, Western blotting, and IHC to validate IGF1R as a target and assess AKT/mTOR pathway activity. Results: Let-7b-5p was significantly downregulated in HCC cells, and its overexpression suppressed proliferation, migration, and enhanced apoptosis. Mechanistically, Let-7b-5p directly targeted IGF1R, leading to reduced phosphorylation of AKT/mTOR, indicating pathway inhibition. Conclusions: Our findings establish Let-7b-5p as a critical regulator of HCC progression via IGF1R-mediated AKT/mTOR suppression, offering a potential therapeutic strategy for HCC treatment.