State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, PR China.
Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, PR China.
Am J Pathol. 2020 Feb;190(2):469-483. doi: 10.1016/j.ajpath.2019.10.010. Epub 2019 Nov 26.
Liver cancer is the third leading cause of cancer-related death worldwide. Herein, we show that miR-149* serves as a novel tumor suppressor for liver tumorigenesis. Mice with genetic deletion of miR-149* (miR-149* mice), which caused loss of both miR-149 and miR-149*, were considerably more susceptible to acute liver injury and hepatic carcinogenesis induced by diethylnitrosamine than wild-type mice, accompanied by increased compensatory proliferation and up-regulated gene expression of certain inflammatory cytokines. miR-149* mimics dramatically impaired liver cancer cell proliferation and migration in vitro and blocked liver cancer progression in a xenograft model. Furthermore, miR-149* strongly suppressed NF-κB signaling and repressed tumor necrosis factor receptor type 1-associated death domain protein expression in the NF-κB signaling pathway. These results reveal that miR-149*, as a novel liver tumor suppressor, may serve as a potential therapeutic target for liver cancer treatment.
肝癌是全球癌症相关死亡的第三大主要原因。在此，我们表明 miR-149* 可作为一种新的肿瘤抑制因子，抑制肝肿瘤发生。miR-149* 基因缺失的小鼠（miR-149* 小鼠），由于同时缺失 miR-149 和 miR-149*，对二乙基亚硝胺诱导的急性肝损伤和肝致癌作用更为敏感，伴随着代偿性增殖增加和某些炎症细胞因子的基因表达上调。miR-149* 模拟物在体外显著抑制肝癌细胞的增殖和迁移，并在异种移植模型中阻断肝癌进展。此外，miR-149* 强烈抑制 NF-κB 信号通路，并抑制肿瘤坏死因子受体 1 相关死亡结构域蛋白在 NF-κB 信号通路中的表达。这些结果表明，miR-149* 作为一种新的肝肿瘤抑制因子，可能成为治疗肝癌的潜在治疗靶点。
