{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:34:02Z","timestamp":1792460042709,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81372903"],"award-info":[{"award-number":["81372903"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>\n                    <jats:sc>Abstract<\/jats:sc>\n                  <\/jats:title>\n                  <jats:p>\n                    Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1) and glucose transporter 1 (Glut\u20101) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K\/Akt\/mTOR pathway. Inhibition of PI3K\/Akt\/mTOR activity abolished hypoxia\u2010induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF\u20101\u03b1 and Glut\u20101. Moreover, the PI3K\/Akt\/mTOR pathway was a positive mediator of HIF\u20101\u03b1 and\/or Glut\u20101 in the presence of irradiation. HIF\u20101\u03b1 and\/or Glut\u20101\u00a0knockout significantly reduced cell viability, glucose uptake and PI3K\/Akt\/mTOR activity, all of which were induced by hypoxia in the presence of irradiation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    analysis showed that knockout of HIF\u20101\u03b1 and\/or Glut\u20101 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF\u20101\u03b1 and Glut\u20101. HIF\u20101\u03b1 and\/or Glut\u20101\u00a0knockout also abrogated PI3K\/Akt\/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF\u20101\u03b1 and\/or Glut\u20101\u00a0knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K\/Akt\/mTOR pathway.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.17303","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:04:07Z","timestamp":1649819047000},"page":"2881-2894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Effect of Glut\u20101 and HIF\u20101\u03b1 double knockout by CRISPR\/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K\/Akt\/mTOR pathway"],"prefix":"10.1111","volume":"26","author":[{"given":"Yang\u2010Yang","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Otolaryngology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou City 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