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Accumulating evidence suggest that during cancer formation, microRNAs (miRNAs) could regulate such metabolic reprogramming. In the present study, miR\u20109\u20101 was identified as significantly hypermethylated in nasopharyngeal carcinoma (NPC) cell lines and clinical tissues. Ectopic expression of miR\u20109\u20101 inhibited NPC cell growth and glycolytic metabolism, including reduced glycolysis, by reducing lactate production, glucose uptake, cellular glucose\u20106\u2010phosphate levels, and ATP generation in vitro and tumor proliferation in vivo. <jats:italic>HK2<\/jats:italic> (encoding hexokinase 2) was identified as a direct target of miR\u20109\u20101 using luciferase reporter assays and Western blotting. In NPC cells, hypermethylation regulates miR\u20109\u20101 expression and inhibits <jats:italic>HK2<\/jats:italic> translation by directly targeting its 3' untranslated region. MiR\u20109\u20101 overexpression markedly reduced HK2 protein levels. Restoration of HK2 expression attenuated the inhibitory effect of miR\u20109\u20101 on NPC cell proliferation and glycolysis. Fluorescence in situ hybridization results indicated that miR\u20109\u20101 expression was an independent prognostic\u00a0factor in NPC. Our findings revealed the role of the miR\u20109\u20101\/HK2 axis in the metabolic reprogramming of NPC, providing a potential therapeutic strategy for NPC.<\/jats:p>","DOI":"10.1111\/cas.15103","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T05:56:19Z","timestamp":1628747779000},"page":"4127-4138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Methylation\u2010associated silencing of miR\u20109\u20101 promotes nasopharyngeal carcinoma progression and glycolysis via HK2"],"prefix":"10.1111","volume":"112","author":[{"given":"Qian\u2010Lan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Affiliated Hospital of Guilin Medical University Guilin China"},{"name":"Department of Laboratory Animal Center Southern Medical University Guangzhou 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