Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil.
Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, Brazil.
Sci Rep. 2020 Dec 10;10(1):21674. doi: 10.1038/s41598-020-78766-5.
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.
游离 DNA 存在于不同的生物体液中，当肿瘤细胞释放时，可能会促进肿瘤发生，如肿瘤附近细胞的恶性转化和转移。因此，本研究分析了从前列腺癌患者血液中分离的肿瘤游离 DNA 对非肿瘤前列腺细胞系（RWPE-1 和 PNT-2）的影响。为此，我们进行了游离 DNA 定量和特征分析、针对癌症进展和 EMT 的基因和 miRNA 表达谱评估，以及通过质谱和细胞迁移进行代谢组学分析。结果表明，肿瘤游离 DNA 能够改变 MMP9 和 CD44 的基因表达，改变 9 种 miRNA 的表达谱，并增加非肿瘤细胞色氨酸的消耗和迁移率。因此，肿瘤游离 DNA 能够改变受体细胞表型，触发这些细胞中与恶性转化相关的事件，因此可以被认为是癌症诊断和治疗的潜在靶点。
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