Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, 67100 L'Aquila, Italy.
Inno-Sol srl, Via della Ricerca Scientifica snc, ed. PP1, 00133 Rome, Italy.
Genes (Basel). 2021 Oct 28;12(11):1726. doi: 10.3390/genes12111726.
The detection of circulating microRNA (miRNA)-based biomarkers represents an innovative, non-invasive method for the early detection of cancer. However, the low concentration of miRNAs released in body fluids and the difficult identification of the tumor site have limited their clinical use as effective cancer biomarkers. To evaluate if ultrasound treatment could amplify the release of extracellular cancer biomarkers, we treated a panel of prostate cancer (PCa) cell lines with an ultrasound-based prototype and profiled the release of miRNAs in the extracellular space, with the aim of identifying novel miRNA-based biomarkers that could be used for PCa diagnosis and the monitoring of tumor evolution. We provide evidence that US-mediated sonoporation amplifies the release of miRNAs from both androgen-dependent (AD) and -independent (AI) PCa cells. We identified four PCa-related miRNAs, whose levels in LNCaP and DU145 supernatants were significantly increased following ultrasound treatment: mir-629-5p, mir-374-5p, mir-194-5p, and let-7d-5p. We further analyzed a publicly available dataset of PCa, showing that the serum expression of these novel miRNAs was upregulated in PCa patients compared to controls, thus confirming their clinical relevance. Our findings highlight the potential of using ultrasound to identify novel cell-free miRNAs released from cancer cells, with the aim of developing new biomarkers with diagnostic and predictive value.
基于循环 microRNA（miRNA）的生物标志物的检测代表了一种创新的、非侵入性的早期癌症检测方法。然而，由于体液中 miRNA 浓度低，以及肿瘤部位难以识别，它们作为有效的癌症生物标志物的临床应用受到了限制。为了评估超声处理是否可以放大细胞外癌症生物标志物的释放，我们用一种基于超声的原型处理了一组前列腺癌（PCa）细胞系，并对细胞外空间中 miRNA 的释放进行了分析，目的是确定可用于 PCa 诊断和肿瘤演变监测的新型 miRNA 生物标志物。我们提供的证据表明，US 介导的声孔作用放大了依赖雄激素（AD）和非依赖雄激素（AI）PCa 细胞中 miRNA 的释放。我们鉴定了四个与 PCa 相关的 miRNA，它们在 LNCaP 和 DU145 上清液中的水平在超声处理后显著增加：mir-629-5p、mir-374-5p、mir-194-5p 和 let-7d-5p。我们进一步分析了一个公开的 PCa 数据集，显示这些新型 miRNA 在 PCa 患者血清中的表达与对照组相比上调，从而证实了它们的临床相关性。我们的研究结果强调了使用超声识别来自癌细胞的新型无细胞 miRNA 的潜力，旨在开发具有诊断和预测价值的新型生物标志物。
