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The transcriptional regulation of the <jats:italic>miR-483-3p<\/jats:italic> could be driven by the \u03b2-catenin\/USF1 complex, independently from its host gene <jats:italic>IGF2,<\/jats:italic> and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type <jats:italic>TP53<\/jats:italic> the upregulation of the <jats:italic>miR-483-3p<\/jats:italic> overcomes the antitumoral effects of the tumor-suppressor <jats:italic>miR-145-5p<\/jats:italic> by a mechanism involving cellular glucose availability. Here we demonstrate that in HepG2 cells, the molecular link between glucose concentration and <jats:italic>miR-483-3p<\/jats:italic> expression entails the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), which stabilizes the transcriptional complex at the <jats:italic>miR-483<\/jats:italic> promoter. HepG2 cells showed reduced <jats:italic>miR-483-3p<\/jats:italic> expression and increased susceptibility to 5-fluorouracil (5-FU)-induced apoptosis in presence of the inhibitor of glycolysis 2-deoxy-<jats:sc>d<\/jats:sc>-glucose (2-DG). However, <jats:italic>i<\/jats:italic><jats:italic>n vivo<\/jats:italic> experiments showed that HepG2 cells with higher <jats:italic>miR-483-3p<\/jats:italic> expression were selected during tumor progression regardless of 5-FU treatment. Furthermore, treatment with 2-DG alone did not significantly reduce HepG2 xenograft load in immunodeficient mice. In conclusion, we show that in HepG2 cells glucose uptake increases the expression of the oncogenic <jats:italic>miR-483-3p<\/jats:italic> through the OGT pathway. This suggests that depletion of the <jats:italic>miR-483-3p<\/jats:italic> may be a valuable therapeutic approach in liver cancer patients, but the use of inhibitors of glycolysis to achieve this purpose could accelerate the selection of resistant neoplastic cell clones.<\/jats:p>","DOI":"10.1038\/oncsis.2017.35","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T13:21:25Z","timestamp":1494249685000},"page":"e328-e328","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Regulation of miR-483-3p by the O-linked N-acetylglucosamine transferase links chemosensitivity to glucose metabolism in liver cancer cells"],"prefix":"10.1038","volume":"6","author":[{"given":"F","family":"Pepe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Pagotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Lanuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Braconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mariani-Costantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Visone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,8]]},"reference":[{"key":"BFoncsis201735_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM . 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