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

PMCID: PMC12175197

PMID: 40530890

DOI: 10.1002/cam4.71000

Journal: Cancer medicine

Publication Date: 2025-6-18

Authors: Liang J, Li A, Chen J, Cao N, Zhu T, et al.

Key Points

• Let-7b-5p is significantly downregulated in HCC, associated with reduced patient survival (p = 0.04805)
• Overexpression of Let-7b-5p decreased HCC cell proliferation by approximately 80% and increased apoptosis rates
• Targeting IGF1R via Let-7b-5p represents a potential precision medicine approach for HCC treatment

Summary

This comprehensive study investigates the role of microRNA Let-7b-5p in hepatocellular carcinoma (HCC), revealing its potential as a critical tumor suppressor. By systematically analyzing Let-7b-5p expression across HCC tissues and cell lines, researchers demonstrated significant downregulation of this microRNA, which correlates with reduced patient survival rates. Functional experiments demonstrated that Let-7b-5p overexpression substantially inhibits HCC cell proliferation, migration, and promotes apoptosis through targeted suppression of the IGF1R gene and subsequent modulation of the AKT/mTOR signaling pathway.

The mechanistic insights uncovered suggest Let-7b-5p as a promising therapeutic target for HCC management. By directly targeting IGF1R and reducing phosphorylation of key signaling molecules, this microRNA emerges as a potential molecular intervention strategy. The study's findings not only elucidate the complex regulatory mechanisms underlying HCC progression but also provide a foundational framework for developing novel microRNA-based therapeutic approaches that could potentially improve patient outcomes.