外泌体传递的环状 RNA circ-LMO7 通过调控 miR-21-5p/ARHGAP24 轴促进骨肉瘤的进展。

IF 4.4 4区 医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-05-14 DOI:10.1080/15384047.2024.2343450
Anyu Luo, Hanlin Liu, Chen Huang, Sheng Wei
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引用次数: 0

摘要

circRNAs在调控骨肉瘤(OS)细胞恶性表现方面的潜在功能和机制尚未得到很好的研究。本研究采用 RT-qPCR 方法检测了 CircLMO7、miR-21-5p 和 ARHGAP24 的表达水平。通过生物信息学分析和荧光素酶报告基因实验,预测并研究了 miR-21-5p 与 circ-LMO7 以及 miR-21-5p 与 ARHGAP24 之间的关系。此外,还分别使用细胞计数试剂盒-8(CCK-8)、透孔法和流式细胞术检测了 OS 细胞的生长、侵袭、迁移和凋亡。Western印迹法检测了ARHGAP24蛋白水平。本研究选择探究circ-LOM7在OS细胞增殖、迁移和侵袭中的作用和机制。强制表达 circ-LOM7 可抑制 OS 细胞的生长、侵袭和迁移。相反,降低 circ-LMO7 的表达则会产生相反的效果。此外,预计miR-21-5p会被circ-LMO7疏导,并在OS中发挥与circ-LMO7相反的作用。此外,ARHGAP24是miR-21-5p的下游靶标。从机理上讲,circ-LMO7被包裹在外泌体中,通过海绵化miR-21-5p和上调ARHGAP24的表达对OS起到抑癌作用。外泌体circ-LMO7在OS细胞外泌体中的表达明显下降,共培养实验表明外泌体circ-LMO7抑制了OS细胞的增殖能力。Circ-LMO7是OS的肿瘤抑制因子,而circ-LMO7/miR-21-5P/ARHGAP24轴参与了OS的进展。
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Exosome-transmitted circular RNA circ-LMO7 facilitates the progression of osteosarcoma by regulating miR-21-5p/ARHGAP24 axis.

The potential function and mechanism of circRNAs in regulating malignant performances of Osteosarcoma (OS) cells have not been well investigated. The expression level of CircLMO7, miR-21-5p and ARHGAP24 were detected by RT-qPCR. The relationship between miR-21-5p and circ-LMO7, as well as between miR-21-5p and ARHGAP24, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), transwell and flow cytometry assays, respectively. ARHGAP24 protein level was measured using western blotting. In present study, we choose to investigate the role and mechanism of circ-LOM7 on OS cell proliferation, migration and invasion. circ-LOM7 was found to be down-regulated in OS tissues and cell lines. Enforced expression of circ-LOM7 suppressed the growth, invasion, and migration of OS cells. In contrast, decreasing circ-LMO7 expression had opposite effects. Furthermore, miR-21-5p was predicted to be sponged by circ-LMO7, and had an opposite role of circ-LMO7 in OS. Moreover, ARHGAP24 served as miR-21-5p's downstream target. Mechanistically, circ-LMO7 was packed in exosomes and acted as a cancer-suppresser on OS by sponging miR-21-5p and upregulating the expression of ARHGAP24. The exosomal circ-LMO7 expression was significantly decreased in OS cell exosomes, and co-culture experiments showed that exosomal circ-LMO7 suppressed the proliferation ability of OS cells. Circ-LMO7 exerts as a tumor suppressor in OS, and the circ-LMO7/miR-21-5P/ARHGAP24 axis is involved in OS progression.

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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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