miR-10b-5p 通过靶向 SLC38A2 调节肝癌细胞代谢促进肿瘤生长

IF 4.4 4区 医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-02-23 DOI:10.1080/15384047.2024.2315651
Mingzhi Xia, Jie Chen, Yingyun Hu, Bin Qu, Qianqian Bu, Haoming Shen
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引用次数: 0

摘要

代谢重编程在肝癌发生过程中起着至关重要的作用。然而,原发性肝癌(PLC)代谢重编程的调控机制尚不清楚。通过生物信息学分析确定了原发性肝癌和正常组织中表达不同的 miRNA。采用 RT-qPCR 确定 miR-10b-5p 和 SCL38A2 的表达水平。采用 IHC、WB 和 TUNEL 检测法评估组织的增殖和凋亡。利用 CCK-8 试验、Transwell 试验和流式细胞术测定了 PLC 细胞的增殖、迁移、侵袭和凋亡。使用双荧光素酶报告实验测定了 miR-10b-5p 与 SLC38A2 之间的相互作用。在 BALB/c 裸鼠中建立了 PLC 异种移植模型,并对其致瘤性和 SLC38A2 表达进行了评估。最后,利用液相色谱-质谱(LC-MS)非靶向代谢组学分析了裸鼠异种移植 PLC 组织的代谢谱。与癌旁组织相比,miR-10b-5p在肿瘤组织中的表达增加。从机制上看,miR-10b-5p靶向SLC38A2,促进了PLC肿瘤的生长。此外,miR-10b-5p 还改变了 PLC 在体内的代谢特征。通过靶向 SLC38A2,miR-10b-5p 促进了 PLC 的代谢重编程,最终促进了 PLC 细胞的增殖、迁移和侵袭。因此,miR-10b-5p 和 SLC38A2 是诊断和治疗 PLC 的潜在靶点。
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miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2.

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 in vivo. 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.

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来源期刊
Cancer Biology & Therapy
Cancer Biology & Therapy 医学-肿瘤学
CiteScore
7.00
自引率
0.00%
发文量
60
审稿时长
2.3 months
期刊介绍: Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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