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The Potential Therapeutic Role of Exosomal MicroRNA-520b Derived from Normal Fibroblasts in Pancreatic Cancer

机译:正常成纤维细胞来源的外泌体MicroRNA-520b在胰腺癌中的潜在治疗作用

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摘要

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 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 . 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.
机译:胰腺癌(PC)仍然是主要的健康问题,常规的癌症治疗对疾病进程的影响很小。 MicroRNA-520b(miR-520b)在几种类型的人类癌症中起着抑癌作用,而在PC领域,其抗肿瘤特性仍然至关重要。这项研究的目的是确定由外泌体转移的,源自正常成纤维细胞(NFs)的miR-520b在PC进展中的潜在治疗作用。进行了一项功能增益研究,以检查miR-520b在PC细胞系SW1990中的作用,这表明miR-520b在PC中起着抑癌作用。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。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,迁移和刺激细胞凋亡。此外,观察到在外泌体中miR-520b升高会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的发展,这有助于外泌体miR-520b用于治疗PC的新型治疗作用。

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