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MicroRNAs (miRNAs), and particularly circulating miRNAs, regulate multiple cellular functions, and their deregulation has been reported in different types of cancer and metastasis. However, their signature in plasma along brain metastasis development and their relevant targets remain undetermined. Here, we used a mouse model of BCBM and next\u2010generation sequencing (NGS) to establish the alterations in circulating miRNAs during brain metastasis formation and development. We further performed bioinformatics analysis to identify their targets with relevance in the metastatic process. We additionally analyzed human resected brain metastasis samples of breast cancer patients for target expression validation. Breast cancer cells were injected in the carotid artery of mice to preferentially induce metastasis in the brain, and samples were collected at different timepoints (5\u00a0h, 3, 7, and 10\u00a0days) to follow metastasis development\u00a0in the brain and in peripheral organs. Metastases were detected from 7\u00a0days onwards, mainly in the brain. NGS revealed a deregulation of circulating miRNA profile during BCBM progression, rising from 18% at 3\u00a0days to 30% at 10\u00a0days following malignant cells\u2019 injection. Work was focused on those altered prior to metastasis detection, among which were miR\u2010802\u20105p and miR\u2010194\u20105p, whose downregulation was validated by qPCR. Using <jats:sc>targetscan<\/jats:sc> and <jats:sc>diana tools<\/jats:sc>, the transcription factor myocyte enhancer factor 2C (MEF2C) was identified as a target for both miRNAs, and its expression was increasingly observed in malignant cells along brain metastasis development. Its upregulation was also observed in peritumoral astrocytes pointing to a role of MEF2C in the crosstalk between tumor cells and astrocytes. MEF2C expression was also observed in human BCBM, validating the observation in mouse. Collectively, downregulation of circulating miR\u2010802\u20105p and miR\u2010194\u20105p appears as a precocious event in BCBM and MEF2C emerges as a new player in brain metastasis development.<\/jats:p>","DOI":"10.1002\/1878-0261.12632","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T10:47:20Z","timestamp":1578912440000},"page":"520-538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Downregulation of circulating miR 802\u20105p and miR 194\u20105p and upregulation of brain MEF2C along breast cancer brain metastasization"],"prefix":"10.1002","volume":"14","author":[{"given":"Marta","family":"Sereno","sequence":"first","affiliation":[{"name":"Faculdade de Farm\u00e1cia Research Institute for Medicines (iMed.ULisboa) Universidade de Lisboa Portugal"}]},{"given":"J\u00e1nos","family":"Hask\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Biophysics 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