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Here, we identify the newly evolved human microRNA miR\u20106762\u20105p as a new player in the host\u2013<jats:italic>Shigella<\/jats:italic> interplay. A microarray analysis in infected epithelial cells allowed the detection of this miRNA exclusively during the late phase of infection. Conditional expression of miR\u20106762\u20105p combined with a transcriptome analysis indicated a role in cytoskeleton remodeling. Likewise, miR\u20106762\u20105p enhanced stress fiber formation through RhoA activation, and <jats:italic>in silico<\/jats:italic> analysis identified several regulators of RhoA activity as potential direct transcriptional targets. We further showed that miR\u20106762\u20105p expression induces an increase in <jats:italic>Shigella<\/jats:italic> intercellular spreading, while miR\u20106762\u20105p inhibition reduced bacterial dissemination. We propose a model in which the expression of miR\u20106762\u20105p induces cytoskeleton modifications through RhoA activation to achieve a successful dissemination of <jats:italic>Shigella<\/jats:italic> in the host.<\/jats:p>","DOI":"10.1111\/mmi.15352","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:41:51Z","timestamp":1741732911000},"page":"420-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Human\u2010Specific <scp>miR<\/scp>\u20106762\u20105p Is an Activator of <scp>RhoA GTPase<\/scp> Enhancing <scp><i>Shigella flexneri<\/i><\/scp> Intercellular Spreading"],"prefix":"10.1111","volume":"123","author":[{"given":"Caroline","family":"Reisacher","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, Institut Necker Enfants Malades  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Saifi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, Institut Necker Enfants Malades  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Ageron","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, Institut Necker Enfants Malades  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Theodor","family":"Mallmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Und Klinische Pharmakologie Und Toxikologie, Fakult\u00e4t f\u00fcr Medizin Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Klugbauer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Und Klinische Pharmakologie Und Toxikologie, Fakult\u00e4t f\u00fcr Medizin Albert\u2010Ludwigs\u2010Universit\u00e4t Freiburg  Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Skurnik","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, Institut Necker Enfants Malades  Paris France"},{"name":"Service de Microbiologie Clinique AP\u2010HP, H\u00f4pital Necker Enfants Malades  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-346X","authenticated-orcid":false,"given":"Laurence","family":"Arbibe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, CNRS, Institut Necker Enfants Malades  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0614-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02952.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.34.20246"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049625"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3867"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10607-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019104058"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2005.00335.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108409"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3485"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01148"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.03.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.258767"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa942"},{"key":"e_1_2_8_16_1","first-page":"D498","article-title":"The Reactome Pathway Knowledgebase","volume":"48","author":"Jassal B.","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.107953"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.133553.111"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12202"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5429.895"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00035"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.13.2069"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-022-00145-z"},{"key":"e_1_2_8_24_1","unstructured":"Rasband W. 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