Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models
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 degra...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120300706 |
| _version_ | 1818309699164962816 |
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| author | Ludmila A. Alekseeva Aleksandra V. Sen’kova Marina A. Zenkova Nadezhda L. Mironova |
| author_facet | Ludmila A. Alekseeva Aleksandra V. Sen’kova Marina A. Zenkova Nadezhda L. Mironova |
| author_sort | Ludmila A. Alekseeva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T07:34:19Z |
| format | Article |
| id | doaj.art-c073b435162f49aabf5462aa84315286 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-13T07:34:19Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c073b435162f49aabf5462aa843152862022-12-21T23:55:08ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-06-01205061Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor ModelsLudmila A. Alekseeva0Aleksandra V. Sen’kova1Marina A. Zenkova2Nadezhda L. Mironova3Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, Russia; Corresponding author: Nadezhda L. Mironova, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Avenue, 8, Novosibirsk 630090, Russia.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.http://www.sciencedirect.com/science/article/pii/S2162253120300706circulating cell-free DNASINEsLINEstumormetastasishorizontal transfer |
| spellingShingle | Ludmila A. Alekseeva Aleksandra V. Sen’kova Marina A. Zenkova Nadezhda L. Mironova Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models Molecular Therapy: Nucleic Acids circulating cell-free DNA SINEs LINEs tumor metastasis horizontal transfer |
| title | Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models |
| title_full | Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models |
| title_fullStr | Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models |
| title_full_unstemmed | Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models |
| title_short | Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models |
| title_sort | targeting circulating sines and lines with dnase i provides metastases inhibition in experimental tumor models |
| topic | circulating cell-free DNA SINEs LINEs tumor metastasis horizontal transfer |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120300706 |
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