Hong Jie, Liu Jie, Zhang Yanan, Ding Lihua, Ye Qinong
Medical School of Guizhou University, Guiyang, China.
Department of Cell Engineering, Beijing Institute of Biotechnology, Beijing, China.
Cancer Cell Int. 2023 Apr 11;23(1):66. doi: 10.1186/s12935-023-02915-9.
Reprogrammed lipid metabolism is a hallmark of cancer that provides energy, materials, and signaling molecules for rapid cancer cell growth. Cancer cells acquire fatty acids primarily through de novo synthesis and uptake. Targeting altered lipid metabolic pathways is a promising anticancer strategy. However, their regulators have not been fully investigated, especially those targeting both synthesis and uptake.
Immunohistochemistry was performed on samples from patients with hepatocellular carcinoma (HCC) to establish the correlation between miR-3180, stearoyl-CoA desaturase-1 (SCD1), and CD36 expression, quantified via qRT-PCR and western blotting. The correlation was analyzed using a luciferase reporter assay. Cell proliferation, migration, and invasion were analyzed using CCK-8, wound healing, and transwell assays, respectively. Oil Red O staining and flow cytometry were used to detect lipids. Triglycerides and cholesterol levels were analyzed using a reagent test kit. CY3-labeled oleic acid transport was analyzed using an oleic acid transport assay. Tumor growth and metastasis were detected in vivo in a xenograft mouse model.
MiR-3180 suppressed de novo fatty acid synthesis and uptake by targeting the key lipid synthesis enzyme SCD1 and key lipid transporter CD36. MiR-3180 suppressed HCC cell proliferation, migration, and invasion in an SCD1- and CD36-dependent manner in vitro. The mouse model demonstrated that miR-3180 inhibits HCC tumor growth and metastasis by inhibiting SCD1- and CD36-mediated de novo fatty acid synthesis and uptake. MiR-3180 expression was downregulated in HCC tissues and negatively correlated with SCD1 and CD36 levels. Patients with high miR-3180 levels showed better prognosis than those with low levels.
Our investigation indicates that miR-3180 is a critical regulator involved in de novo fatty acid synthesis and uptake, which inhibits HCC tumor growth and metastasis by suppressing SCD1 and CD36. Therefore, miR-3180 is a novel therapeutic target and prognostic indicator for patients with HCC.
重编程的脂质代谢是癌症的一个标志，为癌细胞的快速生长提供能量、物质和信号分子。癌细胞主要通过从头合成和摄取来获取脂肪酸。靶向改变的脂质代谢途径是一种有前景的抗癌策略。然而，其调节因子尚未得到充分研究，尤其是那些同时靶向合成和摄取的调节因子。
对肝细胞癌（HCC）患者的样本进行免疫组织化学，以建立miR-3180、硬脂酰辅酶A去饱和酶-1（SCD1）和CD36表达之间的相关性，并通过qRT-PCR和蛋白质印迹法进行定量。使用荧光素酶报告基因检测分析相关性。分别使用CCK-8、伤口愈合和Transwell检测分析细胞增殖、迁移和侵袭。使用油红O染色和流式细胞术检测脂质。使用试剂检测试剂盒分析甘油三酯和胆固醇水平。使用油酸转运检测分析CY-标记的油酸转运。在异种移植小鼠模型中体内检测肿瘤生长和转移。
MiR-3180通过靶向关键脂质合成酶SCD1和关键脂质转运蛋白CD36抑制从头脂肪酸合成和摄取。MiR-3180在体外以SCD1和CD36依赖的方式抑制HCC细胞增殖、迁移和侵袭。小鼠模型表明，miR-3180通过抑制SCD1和CD36介导的从头脂肪酸合成和摄取来抑制HCC肿瘤生长和转移。MiR-3180在HCC组织中的表达下调，且与SCD1和CD36水平呈负相关。miR-3180水平高的患者比水平低的患者预后更好。
我们的研究表明，miR-3180是参与从头脂肪酸合成和摄取的关键调节因子，通过抑制SCD1和CD36来抑制HCC肿瘤生长和转移。因此，miR-3180是HCC患者的新型治疗靶点和预后指标。
