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细胞外囊泡介导的 PC3 细胞向巨噬细胞转移 miRNA Let-7b。

Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages.

机构信息

Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy.

Faculty of Psycology, Università degli Studi eCampus, 22060 Novedrate, Italy.

出版信息

Genes (Basel). 2020 Dec 12;11(12):1495. doi: 10.3390/genes11121495.

Abstract

Prostate-derived extracellular vesicles (pEVs) may represent a way to selectively transport cargo molecules from the producing cells to the target cells to allow biological events, both in physiological and pathological circumstances. pEVs cargo participates in the modulation of the inflammatory responses in physiological conditions and during cancer progression. In the present study, we examined the expression levels of miRNA Let-7b, in both precursor and mature forms, in noncancerous and cancerous prostate cell lines, PNT2 and PC3 respectively, and in their extracellular vesicles (EVs) using reverse-transcription quantitative PCR strategies. We showed that miRNA Let-7b was highly expressed in noncancerous cells and strongly decreased in cancerous PC3 cells, while the opposite was observed in the respective EVs, thus supporting the tumor suppressor role of miRNA Let7-b. We also demonstrated that miRNA Let-7b can be transferred to THP-1 cells via EVs, which are known to induce TAM-like polarization. Our results support the view that miRNA Let-7 b, contained in PC3-derived EVs, is associated with the increase in the miRNA Let7-b observed in TAM-like macrophages. Overall, our results indicate that circulating EV-loaded miRNA might be useful biomarkers for prostate cancer progression and might also support a possible use of pEVs as targets for prostate cancer therapy.

摘要

前列腺细胞外囊泡(pEVs)可能代表了一种从产生细胞中选择性运输货物分子到靶细胞的方式,从而允许在生理和病理情况下发生生物事件。pEVs 的货物参与了在生理条件下和癌症进展过程中炎症反应的调节。在本研究中,我们使用逆转录定量 PCR 策略,分别检查了非癌性和癌性前列腺细胞系 PNT2 和 PC3 及其细胞外囊泡(EVs)中前体和成熟形式的 miRNA Let-7b 的表达水平。我们表明,miRNA Let-7b 在非癌性细胞中高度表达,并在癌性 PC3 细胞中强烈降低,而在相应的 EVs 中则观察到相反的情况,从而支持 miRNA Let7-b 的肿瘤抑制作用。我们还证明,miRNA Let-7b 可以通过 EV 转移到 THP-1 细胞中,已知 EV 可诱导 TAM 样极化。我们的结果支持这样一种观点,即源自 PC3 的 EV 中包含的 miRNA Let-7b 与在 TAM 样巨噬细胞中观察到的 miRNA Let7-b 的增加有关。总的来说,我们的结果表明,循环 EV 负载的 miRNA 可能是前列腺癌进展的有用生物标志物,也可能支持将 pEVs 用作前列腺癌治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e496/7763145/c2cafa65b854/genes-11-01495-g001.jpg

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