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miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric cancer

机译:源自骨髓间充质干细胞的外泌体的miRNA-221促进胃癌的致癌活性

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摘要

Worldwide, gastric cancer (GC) is one of the deadliest malignant tumors of the digestive system. Moreover, microRNAs (miRNAs) of exosomes harbored within cancer cells have been determined to induce inflammatory conditions that accelerate tumor growth and metastasis. Interestingly, the oncogenic role of bone marrow mesenchymal stem cells (BM-MSCs) in the modulation of immunosuppression, tumor invasion, and metastasis was discovered to be partly mediated through the secretion of exosomes. In this article, high expression of miRNA-221 (miR-221) in exosomes of the peripheral blood was determined to be positively correlated with the poor clinical prognosis of GC, especially with respect to tumor, node, and metastases stage. Therefore, the expression of miR-221 in exosomes of the peripheral blood may be an important detection index for GC. Proliferation, migration, invasion, and adhesion to the matrix of GC BGC-823 and SGC-7901 cells were significantly enhanced by exosomes that originated from BM-MSCs that were transfected with miR-221 mimics. In conclusion, extracted exosomes from BM-MSCs transfected with miR-221 oligonucleotides can act as high-efficiency nanocarriers, which can provide sufficient miR-221 oligonucleotides to influence the tumor microenvironment and tumor aggressiveness effectively. Notably, the use of a miR-221 inhibitor with an excellent restraining effect in exosomes provides therapeutic potential for GC in future clinical medicine.
机译:在世界范围内,胃癌(GC)是消化系统最致命的恶性肿瘤之一。此外,已经确定了癌细胞中所含外泌体的microRNA(miRNA)可以诱导炎症条件,从而加速肿瘤的生长和转移。有趣的是,发现骨髓间充质干细胞(BM-MSC)在调节免疫抑制,肿瘤侵袭和转移中的致癌作用部分是通过外泌体的分泌介导的。在本文中,确定外周血外泌体中miRNA-221(miR-221)的高表达与GC不良的临床预后呈正相关,特别是在肿瘤,淋巴结和转移阶段方面。因此,miR-221在外周血外泌体中的表达可能是GC的重要检测指标。源自被miR-221模拟物转染的BM-MSC的外来体显着增强了GC BGC-823和SGC-7901细胞的增殖,迁移,侵袭以及对基质的粘附。总之,从miR-221寡核苷酸转染的BM-MSC中提取的外泌体可以作为高效的纳米载体,可以提供足够的miR-221寡核苷酸来有效地影响肿瘤的微环境和侵袭性。值得注意的是,在外泌体中使用具有优异抑制作用的miR-221抑制剂可为将来的临床医学中的GC提供治疗潜力。

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