微小RNA Let-7b-5p通过AKT/mTOR途径靶向胰岛素样生长因子1受体（IGF1R）以抑制肝细胞癌进展。
MicroRNA Let-7b-5p Targets IGF1R to Inhibit the Progression of Hepatocellular Carcinoma Through the AKT/mTOR Pathway.
作者信息
Liang Jiaojiao, Li Amin, Chen Jun, Cao Niandie, Zhu Tao, Cai Ru, Zhou Shuping, Liang Yong, Tang Xiaolong
机构信息
The First Affiliated Hospital of Anhui University of Science & Technology (Huainan First People's Hospital), Huainan, China.
Medical College, Anhui University of Science & Technology, Huainan, China.
出版信息
Cancer Med. 2025 Jun;14(12):e71000. doi: 10.1002/cam4.71000.
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.
背景
肝细胞癌（HCC）仍然是全球主要的健康负担，微小RNA Let-7b-5p（Let-7b-5p）作为一种潜在的肿瘤抑制因子逐渐显现。然而，其在HCC进展中的精确作用和分子机制仍不清楚，需要进一步研究。
方法
我们通过qRT-PCR评估了HCC与正常肝细胞中Let-7b-5p的表达，并采用功能分析（克隆形成、EdU、划痕、Transwell、凋亡）来研究其对增殖、迁移和细胞死亡的影响。机制研究结合生物信息学、蛋白质印迹法和免疫组化来验证IGF1R作为靶点并评估AKT/mTOR信号通路活性。
结果
Let-7b-5p在HCC细胞中显著下调，其过表达抑制了增殖、迁移并增强了凋亡。机制上，Let-7b-5p直接靶向IGF1R，导致AKT/mTOR磷酸化减少，表明该信号通路受到抑制。
结论
我们的研究结果表明Let-7b-5p通过IGF1R介导的AKT/mTOR抑制作用成为HCC进展的关键调节因子，为HCC治疗提供了一种潜在的治疗策略。
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