肿瘤抑制因子miR-379-5p在胃癌中的内源性和细胞外作用

IF 1.8 3区 医学 Q3 ONCOLOGY
Oncology Pub Date : 2025-05-26 DOI:10.1159/000546620
Michelle Xin Liu, Kent-Man Chu
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引用次数: 0

摘要

mirna在包括胃癌在内的多种癌症的发生发展中发挥着重要作用。外泌体是用于转移分子的细胞外囊泡。本研究旨在探讨miR-379-5p在胃癌中的抑瘤作用,并探讨外泌体在将miR-379-5p从细胞内转运到细胞外中的作用。方法:采集53对胃癌和非肿瘤组织标本。应用了5个细胞系。功能实验包括细胞增殖、细胞迁移和侵袭、细胞粘附实验。通过western blot筛选miR-379-5p的靶点并进行验证。RT-qPCR检测胃癌细胞内源性miR-379-5p和细胞培养基外泌体miR-379-5p的表达。MKN45和HEK293T分别采用培养AGS或BCG23培养基进行培养。结果:结果显示,miR-379-5p在胃癌组织样本和细胞系中显著下调。强制表达miR-379-5p抑制胃癌细胞的增殖、迁移和侵袭,而miR-379-5p模拟增强细胞对细胞外基质的粘附。IGF1R是胃癌中miR-379-5p的潜在靶点。在细胞培养基中,miR-379-5p在外泌体中的表达显著高于其内源表达。来自AGS或BCG23细胞培养基的外泌体可以调节HEK293T细胞内源性miR-379-5p的表达。结论:MiR-379-5p在胃癌中显著下调,发挥抑癌作用。MiR-379-5p在培养基外泌体中的表达高于其内源表达。MiR-379-5p可以从细胞中易位到细胞培养基中,并通过外泌体进入某些细胞类型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Endogenous and Extracellular Roles of a Tumor Suppressor miR-379-5p in Gastric Cancer.

Introduction: MiRNAs play important roles in development of various cancers including gastric cancer. Exosomes are extracellular vesicles for translocating molecules. This study aimed to investigate the tumor suppressive roles of miR-379-5p in gastric cancer and to investigate the roles of exosomes in transporting miR-379-5p from intracellular to extracellular.

Methods: Fifty-three pairs of gastric cancer and non-tumor tissue samples were collected. Five cell lines were applied. Functional assays including cell proliferation, cell migration and invasion, and cell adhesion assay were performed. Targets of miR-379-5p were screened and validated by Western blot. Expressions of endogenous miR-379-5p in gastric cancer cells and exosomal miR-379-5p in cell culture medium were evaluated by RT-qPCR. Medium of culturing AGS or BCG23 was applied for culturing MKN45 and HEK293T.

Results: The results indicated that miR-379-5p was significantly downregulated in gastric cancer tissue samples and cell lines. Enforced expression of miR-379-5p inhibited gastric cancer cell proliferation, migration, and invasion, while miR-379-5p mimic enhanced cell adhesion to extracellular matrix. IGF1R was a potential target of miR-379-5p in gastric cancer. Expression of miR-379-5p was dramatically higher in exosomes in cell culture medium than its endogenous expression. Exosomes from cell culture medium of AGS or BCG23 could regulate endogenous expression of miR-379-5p in HEK293T cells.

Conclusions: MiR-379-5p was significantly downregulated and it functioned as a tumor suppressor in gastric cancer. MiR-379-5p was highly expressed in exosomes of culture medium than its endogenous expression. MiR-379-5p could be translocated from cells into cell culture medium and entered certain cell types via exosomes.

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来源期刊
Oncology
Oncology 医学-肿瘤学
CiteScore
6.00
自引率
2.90%
发文量
76
审稿时长
6-12 weeks
期刊介绍: Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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