肿瘤细胞衍生的细胞外囊泡携带的circ_0064516能竞争性抑制microRNA-6805-3p，促进宫颈癌血管生成和肿瘤生长。

IF 4.6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Therapeutic Targets Pub Date : 2024-01-01 Epub Date: 2024-03-11 DOI:10.1080/14728222.2024.2306353

Yujue Wang, Yao Xie, Xue Wang, Nian Yang, Zhao Wu, Xun Zhang

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引用次数: 0

摘要

研究背景本研究试图阐明肿瘤细胞衍生的外泌体（Exos）-circ_0064516在宫颈癌血管生成和生长中的调控作用：通过生物信息学分析确定了相关的cirRNA和下游靶基因。从宫颈癌细胞株 CaSki 中分离出 Exos，然后与人脐静脉内皮细胞（HUVECs）共培养。然后检测了circ_0064516、miR-6805-3p和MAPK1在HUVECs迁移和血管生成中的作用。此外，还将异种移植的肿瘤移植到裸鼠体内进行体内验证：结果：体外检测验证了 circ_0064516 在宫颈癌细胞中的高表达。Circ_0064516通过与miR-6805-3p结合增加了MAPK1的表达，从而增强了迁移和血管生成。含有circ_0064516的Exos还促进了裸鼠宫颈癌细胞的肿瘤发生：我们证实了携带 circ_0064516 的肿瘤细胞衍生 Exos 通过 miR-6805-3p/MAPK1 在宫颈癌进展中的致癌作用。

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Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth.

Background: The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer.

Research design and methods: Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation.

Results: In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice.

Conclusions: We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.

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来源期刊

Expert Opinion on Therapeutic Targets 医学-药学

CiteScore

8.90

自引率

1.70%

发文量

审稿时长

3 months

期刊介绍： The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.