外泌体circ_001860通过miR-582-5p/ZEB1轴促进结直肠癌进展

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-09-01 DOI:10.1615/critreveukaryotgeneexpr.2024054404
Weizhen Huang, Jun Li, Siwei Zhou, Yi Li, Xia Yuan
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引用次数: 0

摘要

近年来,人们对外泌体循环RNA(circRNA)在多种恶性肿瘤的整个发展过程中的调控作用进行了广泛的研究。然而,关于外泌体循环RNA在结直肠癌(CRC)中的生物学作用和内在机制,仍有许多问题有待研究。研究人员通过差速离心法从血液样本和 CRC 细胞中分离出了外泌体(exo)。此外,还通过Starbase和双荧光素酶报告基因实验确定了circ_001860在CRC中的竞争性内源性RNA(ceRNA)机制。功能增益和缺失实验验证了circ_001860/miR-582-5p/ZEB1对CRC细胞恶性表型的调控作用。通过小鼠实验探讨了circ_001860对CRC异种移植肿瘤模型的治疗作用。从 CRC 血液样本和 CRC 细胞中分离出的外泌体明显富集了 Circ_001860。Circ_001860可以通过外泌体转运到CRC细胞中。通过与 miR-582-5p 竞争性结合,circ_001860 增加了 ZEB1,从而促进了体内肿瘤的形成,并在体外刺激了 CRC 细胞的增殖和转移。通过miR-582-5p/ZEB1轴,外泌体circ_001860促进了CRC的发展。这一发现可能为临床筛查和诊断 CRC 患者提供非侵入性生物标记物。
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Exosomal circ_001860 promotes colorectal cancer progression through miR-582-5p/ZEB1 axis
Extensive research has recently been conducted to investigate the regulating impact of exosomal circular RNAs (circRNAs) in throughout the development of multiple malignancies. Nevertheless, there is still much to learn about the biological roles and underlying mechanisms of exosomal circRNAs in colorectal cancer (CRC). Exosomes (exo) were isolated from blood samples and CRC cells by differential centrifugation. In addition, the competitive endogenous RNA (ceRNA) mechanism of circ_001860 in CRC was determined through Starbase and dual-luciferase reporter gene experiments. Gain and loss of function experiments verified the regulatory effect of circ_001860/miR-582-5p/ZEB1 on the malignant phenotype of CRC cells. The therapeutic effect of circ_001860 on CRC xenograft tumor model was explored through mouse experiment. Circ_001860 was significantly enriched in exo isolated from CRC blood samples and CRC cells. Circ_001860 can be transported into CRC cells via exo. Through competitive binding to miR-582-5p, circ_001860 increased ZEB1, thereby facilitating tumor formation in vivo as well as stimulating CRC cell proliferation and metastasis in vitro. Through the miR-582-5p/ZEB1 axis, exosomal circ_001860 enhanced the advancement of CRC. This finding may offer non-invasive biomarkers for clinical screening and diagnosis of CRC patients.
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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