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The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.omtn.2019.12.029
Huijuan Shi 1 , Hui Li 1 , Tiantian Zhen 1 , Yu Dong 1 , Xiaojuan Pei 2 , Xiangliang Zhang 3
Affiliation  

Pancreatic cancer (PC) remains a major health concern, with conventional cancer treatments exerting little influence on the disease course. MicroRNA-520b (miR-520b) functions as a tumor suppressor in several types of human cancers, whereas its anti-tumor property in the context of PC is still fundamental. The aim of this study is to identify the potential therapeutic role of miR-520b, transferred by exosomes, derived from normal fibroblasts (NFs) in PC progression. A gain-of-function study was performed to examine the roles of miR-520b in PC cell line SW1990, which suggested that miR-520b served as a tumor suppressor in PC. In order to confirm the role of exosomal miR-520b, exosomes were isolated from NF culture medium and cocultured with SW1990 cells. During the coculture experiments, we disrupted exosome secretion and upregulated exosomal miR-520b. The in vitro coculture studies revealed that miR-520b was transferred from NF-derived exosomes to PC cells and thereby suppressed PC cell proliferation, invasion, migration, and stimulated apoptosis. Furthermore, inhibited tumor growth and live metastasis upon elevated miR-520b in exosomes were observed in vivo. Conjointly, our study demonstrates that NF-derived exosomal miR-520b impedes the progression of PC, which contributes to a novel, therapeutic role of exosomal miR-520b for treating PC.



中文翻译:

源自正常成纤维细胞的外泌体 MicroRNA-520b 在胰腺癌中的潜在治疗作用。

胰腺癌 (PC) 仍然是一个主要的健康问题,传统的癌症治疗对疾病进程几乎没有影响。MicroRNA-520b (miR-520b) 在几种类型的人类癌症中充当肿瘤抑制因子,而其在 PC 方面的抗肿瘤特性仍然是基本的。本研究的目的是确定 miR-520b 在 PC 进展中的潜在治疗作用,miR-520b 由外泌体转移,来源于正常成纤维细胞 (NFs)。进行了一项功能获得性研究以检查 miR-520b 在 PC 细胞系 SW1990 中的作用,这表明 miR-520b 在 PC 中充当肿瘤抑制因子。为了确认外泌体 miR-520b 的作用,从 NF 培养基中分离出外泌体并与 SW1990 细胞共培养。在共培养实验中,我们破坏了外泌体分泌并上调了外泌体 miR-520b。这体外共培养研究表明,miR-520b 从 NF 衍生的外泌体转移到 PC 细胞,从而抑制 PC 细胞增殖、侵袭、迁移并刺激细胞凋亡。此外,在体内观察到外泌体中升高的 miR-520b 抑制肿瘤生长和活转移。同时,我们的研究表明,NF 衍生的外泌体 miR-520b 阻碍了 PC 的进展,这有助于外泌体 miR-520b 治疗 PC 的新的治疗作用。

更新日期:2020-01-10
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