1. Prevention of Metastasis by Suppression of Stemness Genes Using a Combination of microRNAs.
- Author
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Nevskaya KV, Pershina AG, Hmelevskaya ES, Efimova LV, Ibragimova MK, Dolgasheva DS, Tsydenova IA, Ufandeev AA, Buyko EE, Perina EA, Gaptulbarova KA, Kravtsova EA, Krivoshchekov SV, Ivanov VV, Guriev AM, Udut EV, and Litviakov NV
- Subjects
- Animals, Mice, Humans, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Neoplastic, Neoplasm Metastasis prevention & control, Cell Proliferation genetics, MicroRNAs genetics, MicroRNAs metabolism, Lung Neoplasms metabolism
- Abstract
We propose an original strategy for metastasis prevention using a combination of three microRNAs that blocks the dedifferentiation of cancer cells in a metastatic niche owing to the downregulation of stemness genes. Transcriptome microarray analysis was applied to identify the effects of a mixture of microRNAs on the pattern of differentially expressed genes in human breast cancer cell lines. Treatment of differentiated CD44
- cancer cells with the microRNA mixture inhibited their ability to form mammospheres in vitro. The combination of these three microRNAs encapsulated into lipid nanoparticles prevented lung metastasis in a mouse model of spontaneous metastasis. The mixture of three microRNAs (miR-195-5p/miR-520a/miR-630) holds promise for the development of an antimetastatic therapeutic that blocks tumor cell dedifferentiation, which occurs at secondary tumor sites and determines the transition of micrometastases to macrometastases.- Published
- 2024
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