Breast Surgery Department I, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. China.
Liver and gallbladder surgery Department I, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P.R. China.
Cancer Biol Ther. 2024 Dec 31;25(1):2315651. doi: 10.1080/15384047.2024.2315651. Epub 2024 Feb 23.
Metabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography - mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC . Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment.
代谢重编程在肝癌发生中起着关键作用。然而，调控原发性肝癌（PLC）代谢重编程的机制尚不清楚。通过生物信息学分析鉴定 PLC 与正常组织之间差异表达的 miRNAs。使用 RT-qPCR 测定 miR-10b-5p 和 SCL38A2 的表达水平。使用免疫组化、WB 和 TUNEL 检测评估组织的增殖和凋亡。使用 CCK-8 测定、Transwell 测定和流式细胞术测定 PLC 细胞的增殖、迁移、侵袭和凋亡。使用双荧光素酶报告基因测定确定 miR-10b-5p 和 SLC38A2 之间的相互作用。在 BALB/c 裸鼠中建立 PLC 异种移植模型，并评估致瘤性和 SLC38A2 表达。最后，使用液相色谱-质谱（LC-MS）非靶向代谢组学分析裸鼠异种移植 PLC 组织的代谢谱。miR-10b-5p 是调控 PLC 的关键分子。与癌旁组织相比，肿瘤组织中 miR-10b-5p 的表达增加。miR-10b-5p 促进 PLC 细胞的增殖、迁移和侵袭。在机制上，miR-10b-5p 靶向 SLC38A2 以促进 PLC 肿瘤生长。此外，miR-10b-5p 改变了 PLC 的代谢特征。miR-10b-5p 的过表达导致亮氨酸、叶酸、辛酰肉碱和 Beta-Nicotinamide adenine dinucleotide 的含量显著增加，而 2-甲基丙醛、甘氨酰-亮氨酸和 2-羟基己酸的含量降低。miR-10b-5p 通过靶向 SLC38A2 促进 PLC 的代谢重编程，从而最终增强 PLC 细胞的增殖、迁移和侵袭。因此，miR-10b-5p 和 SLC38A2 是 PLC 诊断和治疗的潜在靶点。
