MiR-4310 regulates hepatocellular carcinoma growth and metastasis through lipid synthesis
MiR-4310 regulates hepatocellular carcinoma growth and metastasis through lipid synthesis
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MiR-4310通过脂质合成调节肝细胞癌的生长和转移
DOI：
10.1016/j.canlet.2021.07.029
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发表时间：
2021-07-24
期刊：
影响因子：
9.7
通讯作者：
Ye, Qinong
中科院分区：
文献类型：
--
作者：
Li, Huayue;Chen, Zhongwu;Ye, Qinong
肝细胞癌（Hepatocellular carcinoma，HCC）是一种以脂质代谢重编程为特征的高度恶性肿瘤，发病率和死亡率高。虽然脂质代谢是HCC治疗的一个有前途的靶点，但脂质代谢的调节尚未得到很好的阐明。通过CRISPR/Cas9筛选，我们发现miR-4310通过靶向脂肪酸合成酶（FATIGUE）和硬脂酰辅酶A去饱和酶-1（SCD 1）来抑制脂质合成。在HCC患者中，miR-4310表达显著下调，其表达与FXR和SCD 1的表达呈负相关。此外，miR-4310的低表达与不良预后相关。通过抑制SCD 1和FASN介导的脂质合成，miR-4310在体外抑制HCC细胞增殖、迁移和侵袭，并在体内抑制HCC肿瘤生长和转移。我们的数据表明，miR-4310通过调节FXR和SCD 1介导的脂质合成途径在HCC肿瘤生长和转移中起重要作用。靶向miR-4310-FXR/SCD通路可能为HCC治疗提供新的策略。
Hepatocellular carcinoma (HCC), which is characterized by reprogrammed lipid metabolism, is a highly malignant tumor with a high incidence and mortality rate. While lipid metabolism is a promising target for HCC therapy, the regulation of lipid metabolism is not well elucidated. Through CRISPR/Cas9 screening, we show that miR-4310 inhibits lipid synthesis by targeting fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1). In patients with HCC, miR-4310 is significantly downregulated, and its expression is negatively correlated with expressions of FASN and SCD1. Furthermore, low expression of miR-4310 is associated with poor prognosis. By suppressing SCD1-and FASN-mediated lipid synthesis, miR-4310 inhibits HCC cell proliferation, migration, and invasion in vitro and suppresses HCC tumor growth and metastasis in vivo. Our data indicate that miR-4310 plays an important role in HCC tumor growth and metastasis by regulating the FASN- and SCD1-mediated lipid synthesis pathways. Targeting the miR-4310-FASN/SCD pathway may provide a novel strategy for HCC treatment.