外泌体hsa_circ_0017252通过抑制巨噬细胞M2极化减轻胃癌的发展。

IF 4.3 3区 生物学
Human Cell Pub Date : 2022-09-01 Epub Date: 2022-07-07 DOI:10.1007/s13577-022-00739-9
Jin Song, Xiaolong Xu, Shasha He, Ning Wang, Yunjing Bai, Bo Li, Shengsheng Zhang
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引用次数: 9

摘要

胃癌是一种侵袭性的消化系统恶性肿瘤,发病率高。我们之前证明了miR-17-5p可以改变胃癌的肿瘤发生。此外,其他研究表明,circRNAs可以通过海绵吸附各种mirna来调节GC的进展。然而,circRNAs与miR-17-5p在GC中的关联尚未被探索。因此,本研究旨在通过双荧光素酶测定探索各种circRNAs与miR-17-5p之间可能的相互作用。CCK-8法测定细胞活力,Transwell法测定细胞侵袭和迁移。采用定量反转录PCR (RT-qPCR)评估基因表达,采用透射电镜(TEM)和纳米颗粒跟踪分析(NTA)鉴定外泌体。Annexin V/PI染色检测细胞凋亡。这些研究共同揭示了miR-17-5p是circRNA hsa_circ_0017252的靶标,而hsa_circ_0017252在GC组织中显著下调。此外,hsa_circ_0017252过表达通过海绵作用miR-17-5p抑制GC细胞迁移,GC细胞分泌的外泌体hsa_circ_0017252有效抑制巨噬细胞m2样极化,进而抑制GC细胞侵袭。值得注意的是,含有hsa_circ_0017252的外泌体在体内也抑制了GC肿瘤的生长。因此,我们的数据表明,hsa_circ_0017252的过表达通过抑制miR-17-5p来抑制GC恶性肿瘤。此外,GC细胞分泌的外泌体hsa_circ_0017252通过抑制巨噬细胞m2样极化来减缓GC进展。这些发现提高了我们对胃癌的基本认识,并为开发更有效的胃癌治疗开辟了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exosomal hsa_circ_0017252 attenuates the development of gastric cancer via inhibiting macrophage M2 polarization.

Gastric cancer (GC) is an aggressive malignant tumor of the digestive system, with high morbidity rates. We previously demonstrated that miR-17-5p can modify tumorigenesis in GC. In addition, other studies have shown that circRNAs can regulate GC progression by sponging various miRNAs. However, the association between circRNAs and miR-17-5p in GC has not yet been explored. Hence, this study aimed to explore the possible interactions between various circRNAs and miR-17-5p using a dual-luciferase assay. CCK-8 was used to determine cell viability, and a Transwell assay was used to measure cell invasion and migration. Gene expression was assessed using quantitative reverse transcription PCR (RT-qPCR), and exosomes were identified using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Annexin V/PI staining was also used to detect cell apoptosis. These investigations collectively revealed that miR-17-5p is a target of the circRNA hsa_circ_0017252 and hsa_circ_0017252 is significantly downregulated in GC tissues. In addition, the overexpression of hsa_circ_0017252 inhibited GC cell migration by sponging of miR-17-5p, and GC cell-secreted exosomal hsa_circ_0017252 effectively inhibited macrophage M2-like polarization, which in turn suppressed GC cell invasion. Notably, exosomes containing hsa_circ_0017252 also suppressed GC tumor growth in vivo. Thus, our data suggest that the overexpression of hsa_circ_0017252 suppresses GC malignancy by sponging miR-17-5p. In addition, exosomal hsa_circ_0017252 excreted from GC cells attenuated GC progression by suppressing macrophage M2-like polarization. These findings improve our basic understanding of GC and open a novel avenue for developing more effective GC treatments.

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来源期刊
Human Cell
Human Cell 生物-细胞生物学
CiteScore
6.60
自引率
2.30%
发文量
176
期刊介绍: Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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