title: Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells.
abstract: Glutaminolysis that catabolizes glutamine to glutamate plays a critical role in cancer progression. Glutaminase 2 (GLS2) has been reported as a tumor suppressor. Recent studies implied that GLS2 may display its multifunction besides classical metabolic feature by different localizations and potential protein binding domains. Here, we showed that GLS2 expression correlates inversely with stage, vascular invasion, tumor size and poor prognosis in human hepatocellular carcinoma (HCC) tissues. We found that GLS2 significantly represses cell migration, invasion and metastasis of HCC through downregulation of Snail in vitro and in vivo. Moreover, our results demonstrated that GLS2 interacts with Dicer and stabilizes Dicer protein to facilitate miR-34a maturation and subsequently represses Snail expression in a glutaminase activity independent manner. Our findings indicate that non-glutaminolysis function of GLS2 inhibits migration and invasion of HCC cells by repressing the epithelial-mesenchymal transition via the Dicer-miR-34a-Snail axis.
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan; Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Tsang-Chih
authors.initials: TC
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chi-Kuan
authors.initials: CK
authors.lastname: Chen
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Chen
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.affiliation: Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kuang-Tai
authors.initials: KT
authors.lastname: Kuo
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: kuominliang@ntu.edu.tw.
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D002465:Cell Movement; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D055550:Protein Stability; D034622:RNA Interference; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; C408087:DICER1 protein, human; D043244:Ribonuclease III; C586504:GLS2 protein, human; D005972:Glutaminase; D053487:DEAD-box RNA Helicases
keywords: Dicer; Epithelial–mesenchymal transition; Glutaminase 2; Hepatocellular carcinoma cells; Snail