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胃癌细胞衍生的外泌体miRNA-128-3p通过靶向SASH1促进血管生成。

Gastric cancer cell-derived exosomal miRNA-128-3p promotes angiogenesis by targeting SASH1.

作者信息

Yan Hao, Cai Xinyu, Zhang Jianna, Zhao Hongpeng, Wu Hongwen, Zhang Jingbo, Xu Lanzhi, Liu Shizheng, Zang Yuanwei, Fu Shanshan

机构信息

Department of Gastroenterology, Shandong Public Health Clinical Center, Shandong University, Jinan, China.

Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.

出版信息

Front Oncol. 2024 Nov 27;14:1440996. doi: 10.3389/fonc.2024.1440996. eCollection 2024.

Abstract

Exosomes, key components of the tumour microenvironment, can mediate intercellular communication through the delivery of various signalling molecules, including microribonucleic acids (miRNAs), and ultimately participate in regulating the process of tumour development. In this study, we aimed to investigate the reason and mechanism by which exosomal miRNAs derived from gastric cancer cells affect carcinogenesis and metastasis. Among these miRNAs, microRNA-128-3p (miR-128-3p) was highly expressed in serum exosomes isolated from gastric cancer patients, as confirmed by high-throughput sequencing and subsequent experiments. Coculture of gastric cancer-derived exosomes overexpressing miR-128-3p with human umbilical vein endothelial cells (HUVECs) significantly enhanced HUVEC proliferation, migratio n and angiogenesis. Bioinformatics analysis suggested SASH1 as the target gene of miR-128-3p. The dual luciferase assay and Western blot analysis results confirmed that miR-128-3p directly targeted SASH1 to inhibit its expression in HUVECs. Therefore, this study provides preliminary evidence that gastric cancer-derived exosomal miR-128-3p promotes tumour angiogenesis by targeting SASH1, reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-128-3p, and provides new insights into the novel molecular mechanisms regulating metastasis. This study provides further information for understanding the role of gastric cancer-derived exosomal miR-128-3p in cancer progression and to discover new therapeutic targets.

摘要

外泌体是肿瘤微环境的关键组成部分,可通过递送包括微小核糖核酸(miRNA)在内的各种信号分子介导细胞间通讯,并最终参与调节肿瘤发展进程。在本研究中,我们旨在探究胃癌细胞来源的外泌体miRNA影响肿瘤发生和转移的原因及机制。在这些miRNA中,经高通量测序及后续实验证实,微小核糖核酸-128-3p(miR-128-3p)在从胃癌患者分离的血清外泌体中高表达。将过表达miR-128-3p的胃癌来源外泌体与人脐静脉内皮细胞(HUVECs)共培养,显著增强了HUVECs的增殖、迁移和血管生成。生物信息学分析表明SASH1是miR-128-3p的靶基因。双荧光素酶报告基因检测和蛋白质免疫印迹分析结果证实,miR-128-3p直接靶向SASH1以抑制其在HUVECs中的表达。因此,本研究提供了初步证据,表明胃癌来源的外泌体miR-128-3p通过靶向SASH1促进肿瘤血管生成,揭示了癌症来源的外泌体miR-128-3p的潜在诊断和治疗价值,并为调控转移的新分子机制提供了新见解。本研究为理解胃癌来源的外泌体miR-128-3p在癌症进展中的作用及发现新的治疗靶点提供了进一步的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338d/11631727/0c64179875ba/fonc-14-1440996-g001.jpg

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