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Our immunohistochemical and real-time PCR analysis of 208 tongue tumors show overexpression of Matrix Metalloproteinase, MMP10, in 86% of node-positive tongue tumors (<jats:italic>n<\/jats:italic>\u2009=\u200979; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.00001). Additionally, global profiling for non-coding RNAs associated with node-positive tumors reveals that of the 11 significantly de-regulated miRNAs, <jats:italic>miR-944<\/jats:italic> negatively regulates <jats:italic>MMP10<\/jats:italic> by targeting its 3\u2019-UTR. We demonstrate that proliferation, migration, and invasion of tongue cancer cells are suppressed by <jats:italic>MMP10<\/jats:italic> knockdown or <jats:italic>miR-944<\/jats:italic> overexpression. Further, we show that depletion of <jats:italic>MMP10<\/jats:italic> prevents nodal metastases using an orthotopic tongue cancer mice model. In contrast, overexpression of <jats:italic>MMP10<\/jats:italic> leads to opposite effects upregulating epithelial-mesenchymal-transition, mediated by a tyrosine kinase gene, <jats:italic>AXL<\/jats:italic>, to promote nodal and distant metastasis in vivo. Strikingly, <jats:italic>AXL<\/jats:italic> expression is essential and sufficient to mediate the functional consequence of <jats:italic>MMP10<\/jats:italic> overexpression. Consistent with our findings, TCGA-HNSC data suggests overexpression of <jats:italic>MMP10<\/jats:italic> or <jats:italic>AXL<\/jats:italic> positively correlates with poor survival of the patients. In conclusion, our results establish that the <jats:italic>miR-944\/MMP10\/AXL<\/jats:italic>- axis underlies lymph node metastases with potential therapeutic intervention and prediction of nodal metastases in tongue cancer patients.<\/jats:p>","DOI":"10.1038\/s42003-023-04437-6","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T05:02:56Z","timestamp":1673931776000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Role of miR-944\/MMP10\/AXL- axis in lymph node metastasis in tongue cancer"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-3690","authenticated-orcid":false,"given":"Bhasker","family":"Dharavath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin","family":"Butle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Rane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risha","family":"Khandelwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5293-0299","authenticated-orcid":false,"given":"Sujith","family":"Manavalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Thorat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Sonawane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Vaish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Gera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munita","family":"Bal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil K.","family":"D\u2019Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4977-3779","authenticated-orcid":false,"given":"Sudhir","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-4774","authenticated-orcid":false,"given":"Amit","family":"Dutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"4437_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. 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