bmscs来源的外泌体MiR-126-3p通过靶向PTPN9抑制NSCLC细胞的活力

Q2 Medicine Journal of Buon Pub Date : 2021-09-01
Jun Chen, Cheng Ding, Xianzhou Yang, Jun Zhao
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引用次数: 0

摘要

目的:最近的研究表明骨髓间充质干细胞(BMSCs)衍生的外泌体通过携带内源性分子影响肿瘤的进展。目的探讨骨髓间充质干细胞来源的外泌体携带丰富的微核糖核酸(miR)-126-3p在非小细胞肺癌(NSCLC)中的作用。方法:首先用miR-126-3p转染A549细胞,检测miR-126-3p在A549细胞中的作用。接下来,将miR-126-3p转染到骨髓间充质干细胞中,通过超离心分离BMSCs来源的过表达miR-126-3p的外泌体(Exo-miR-126-3p)。之后,将A549细胞与Exo-miR-126-3p共孵育,检测Exo-miR-126-3p对细胞增殖、迁移、侵袭和凋亡的影响。此外,通过生物信息学分析和双荧光素酶报告基因分析,证实了miR-126-3p与蛋白酪氨酸磷酸酶非受体9型(PTPN9)之间的靶向关系。Western blotting (WB)检测A549细胞中PTPN9及相关蛋白的表达。此外,通过慢病毒包装的miR-126-3p在体内分析了BMSCs外泌体中过表达的miR-126-3p对NSCLC细胞肿瘤生长和凋亡的影响。结果:过表达miR-126-3p抑制体外A549细胞的活力、迁移和侵袭。外泌体含量分析结果显示,miR-126-3p可通过负调控PTPN9介导外泌体对A549细胞的抑制作用。值得注意的是,来自骨髓间充质干细胞的过表达miR-126-3p在体内抑制了肿瘤的生长和凋亡。综上所述,本研究的关键发现表明,bmscs来源的外泌体过表达miR-126-3p可通过负调控PTPN9抑制NSCLC的进展。
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BMSCs-Derived Exosomal MiR-126-3p Inhibits the Viability of NSCLC Cells by Targeting PTPN9.

Purpose: Recent studies have manifested that bone marrow mesenchymal stem cells (BMSCs) derived exosomes affect the progression of tumors through carrying endogenous molecules. To explore the role of BMSCs-derived exosomes carrying abundant micro ribonucleic acid (miR)-126-3p in non-small-cell lung cancer (NSCLC).

Methods: Firstly, A549 cells were transfected with miR-126-3p to detect the role of miR-126-3p in A549 cells. Next, miR-126-3p was transfected into BMSCs, and BMSCs-derived exosomes with over-expressed miR-126-3p (Exo-miR-126-3p) were isolated through ultracentrifugation. After that, A549 cells were co-incubated with Exo-miR-126-3p to determine the effects of Exo-miR-126-3p on cell proliferation, migration, invasion, and apoptosis. Besides, the targeted relationship between miR-126-3p and protein tyrosine phosphatase non-receptor type 9 (PTPN9) was confirmed via bioinformatics analysis and dual-luciferase reporter gene analysis. Western blotting (WB) was employed to measure the expressions of PTPN9 and related proteins in A549 cells. Additionally, the effects of over-expressed miR-126-3p derived from BMSCs exosomes on tumor growth and apoptosis of NSCLC cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo.

Results: Overexpressed miR-126-3p suppressed the viability, migration, and invasion of A549 cells in vitro. Based on the results of exosome content analysis, miR-126-3p could mediate the inhibitory effect of exosomes on A549 cells by negative regulation of PTPN9. Notably, over-expressed miR-126-3p derived from BMSCs inhibited the tumor growth and apoptosis in vivo.

Conclusions: Taken together, the key finding of the study indicated that over-expressed BMSCs-derived exosomal miR-126-3p can suppress the progression of NSCLC through negatively regulating PTPN9.

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来源期刊
Journal of Buon
Journal of Buon 医学-肿瘤学
自引率
0.00%
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0
审稿时长
4-8 weeks
期刊介绍: JBUON aims at the rapid diffusion of scientific knowledge in Oncology. Its character is multidisciplinary, therefore all aspects of oncologic activities are welcome including clinical research (medical oncology, radiation oncology, surgical oncology, nursing oncology, psycho-oncology, supportive care), as well as clinically-oriented basic and laboratory research, cancer epidemiology and social and ethical aspects of cancer. Experts of all these disciplines are included in the Editorial Board. With a rapidly increasing body of new discoveries in clinical therapeutics, the molecular mechanisms that contribute to carcinogenesis, advancements in accurate and early diagnosis etc, JBUON offers a free forum for clinicians and basic researchers to make known promptly their achievements around the world. With this aim JBUON accepts a broad spectrum of articles such as editorials, original articles, reviews, special articles, short communications, commentaries, letters to the editor and correspondence among authors and readers. JBUON keeps the characteristics of its former paper print edition and appears as a bimonthly e-published journal with continuous volume, issue and page numbers.
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