title: Inhibition of HIF-1α Affects Autophagy Mediated Glycosylation in Oral Squamous Cell Carcinoma Cells.
abstract: Purpose. To validate the function of autophagy with the regulation of hypoxia inhibitor-induced glycosylation in oral squamous cell carcinoma cell. Methods. Human Tca8113 cell line was used to detect autophagy and glycosylation related protein expression by western blotting and immunofluorescence with HIF-1α inhibitor. Short interfering RNA (siRNA) transfection blocked human ATG12 and ATG1. Results. HIF-1α inhibitor PX-478 reduced the amount of LC3-II and LC3-I in Tca8113 cells. PX-478 decreased the expression of O-GlcNAc and OGT and increased OGA expression. The tendency of O-GlcNAc showed a similar pattern to OGT. PX-478 gradually decreased OGT expression in Tca8113 cells. Protein level of O-GlcNAc and OGT increased in ATG12 and ATG1 depletion. The expression of OGT decreased at first and then rose slowly with the treatment of Atg12 and Atg1 siRNA and PX-478 fluctuant. Autophagy affected the stability of OGT when HIF-1α signaling was blocked. Conclusions. Autophagy reduced by hypoxic stress inhibited. HIF-1α inhibitor decreased glycosylation. OGT became unstable in the absence of autophagy when HIF-1α signaling was blocked.
authors.affiliation: Department of Pathology, Stomatology Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Li
authors.affiliation: Department of Pathology, Stomatology Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
authors.forename: Ji-An
authors.initials: JA
authors.lastname: Hu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Stomatology Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Wang
mesh_terms: D001343:Autophagy; D000071192:Autophagy-Related Protein 12; D000071189:Autophagy-Related Protein-1 Homolog; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D009150:Mustard Compounds / Q000494:pharmacology; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010666:Phenylpropionates / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C492908:2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide; C466624:ATG12 protein, human; D000071192:Autophagy-Related Protein 12; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009150:Mustard Compounds; D010666:Phenylpropionates; D025841:Small Ubiquitin-Related Modifier Proteins; D017351:N-Acetylglucosaminyltransferases; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human