Tumor-associated cell-free DNAs (cfDNAs) are found to play some important roles at different stages of tumor progression; they are involved in the transformation of normal cells and contribute to tumor migration and invasion. DNase I is considered a promising cancer cure, due to its ability to degrade cfDNAs. Previous studies using murine tumor models have proved the high anti-metastatic potential of DNase I. Later circulating cfDNAs, especially tandem repeats associated with short-interspersed nuclear elements (SINEs) and long-interspersed nuclear elements (LINEs), have been found to be the enzyme’s main molecular targets. Here, using Lewis lung carcinoma, melanoma B16, and lymphosarcoma RLS₄₀ murine tumor models, we reveal that tumor progression is accompanied by an increase in the level of SINE and LINEs in the pool of circulating cfDNAs. Treatment with DNase I decreased in the number and area of metastases by factor 3–10, and the size of the primary tumor node by factor 1.5–2, which correlated with 5- to 10-fold decreasing SINEs and LINEs. We demonstrated that SINEs and LINEs from cfDNA of tumor-bearing mice are able to penetrate human cells. The results show that SINEs and LINEs could be important players in metastasis, and this allows them to be considered as attractive new targets for anticancer therapy.

发现与肿瘤相关的无细胞DNA（cfDNA）在肿瘤进展的不同阶段起着重要作用。它们参与正常细胞的转化，并有助于肿瘤的迁移和侵袭。DNase I由于其降解cfDNA的能力而被认为是有前途的癌症治疗方法。先前使用鼠类肿瘤模型进行的研究证明了DNase I具有很高的抗转移潜力。后来发现循环cfDNAs，尤其是与短散布的核元件（SINEs）和长散布的核元件（LINEs）相关的串联重复序列是酶的主要分子靶标。在这里，使用Lewis肺癌，黑色素瘤B16和淋巴肉瘤RLS ₄₀在鼠类肿瘤模型中，我们发现肿瘤进展伴随循环cfDNA池中SINE和LINEs水平的增加。DNase I的治疗使转移的数目和面积减少了3-10倍，而原发肿瘤结节的大小减少了1.5-2倍，这与SINE和LINE降低5到10倍相关。我们证明，来自荷瘤小鼠cfDNA的SINE和LINEs能够穿透人类细胞。结果表明，SINE和LINEs可能是转移的重要因素，这使它们成为抗癌治疗的有吸引力的新靶标。