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过表达 miR-1228 的骨髓间充质干细胞来源的外泌体促进胃癌细胞的生长。

Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells.

机构信息

Department of Gastroenterology, The First Ward, Shijiazhuang First Hospital, Shijiazhuang, Hebei Province, China.

Department of General Practice, Shijiazhuang First Hospital, Shijiazhuang, Hebei Province, China.

出版信息

Aging (Albany NY). 2021 Apr 21;13(8):11808-11821. doi: 10.18632/aging.202878.

Abstract

There has been increasing evidence that microRNAs (miRNAs) are related to glioma progression, and that genetically engineered mesenchymal stem cells (MSCs) can inhibit the growth of gliomas. However, the underlying mechanism of bone marrow-MSCs (BM--MSCs) and miRs in gastric cancer still remains unclear. Patients with gastric cancer treated in Shijiazhuang First Hospital as well as healthy individuals undergoing physical examinations were recruited to measure the expression of exosomal miR-1228. Receiver operating characteristic (ROC) curves were plotted and the patients were followed up. BM--MSCs from healthy subjects were collected and exosomes were extracted. The MSC cells were transfected with lentiviral vectors carrying miR-1228 and MMP-14 over-expression sequences and scramble sequence, followed by exosome extraction. The exosomes were co-cultured with SGC-7901 and MGC-823 cells to detect cell proliferation, invasion, apoptosis and migration. The correlation between miR-1228 and MMP-14 was determined by dual-luciferase reporter assay. miR-1228 was highly expressed in serum exosomes of patients with gastric cancer with a area under ROC curve (AUC) of 0.865. The exosomes derived from BM-MSCs are expected to be efficient nanocarriers. Up-regulation of miR-1228 can down-regulate the expression of MMP-14 and effectively hinders the development and progression of gastric cancer.

摘要

越来越多的证据表明 microRNAs(miRNAs)与胶质瘤的进展有关,并且基因工程间充质干细胞(MSCs)可以抑制胶质瘤的生长。然而,骨髓间充质干细胞(BM-MSCs)和 miR 在胃癌中的潜在机制仍不清楚。本研究招募了在石家庄市第一医院治疗的胃癌患者和接受体检的健康个体,以测量外泌体 miR-1228 的表达。绘制了受试者工作特征(ROC)曲线并对患者进行了随访。从健康受试者中收集 BM-MSCs 并提取外泌体。将 MSC 细胞用携带 miR-1228 和 MMP-14 过表达序列和乱序序列的慢病毒载体转染,然后提取外泌体。将外泌体与 SGC-7901 和 MGC-823 细胞共培养,以检测细胞增殖、侵袭、凋亡和迁移。通过双荧光素酶报告基因检测确定 miR-1228 和 MMP-14 之间的相关性。胃癌患者血清外泌体中 miR-1228 高表达,ROC 曲线下面积(AUC)为 0.865。BM-MSCs 衍生的外泌体有望成为有效的纳米载体。上调 miR-1228 可以下调 MMP-14 的表达,并有效抑制胃癌的发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a1/8109060/dc9a6ac4f1bf/aging-13-202878-g001.jpg

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