title: Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma.
abstract: OBJECTIVE
  Oral squamous cell carcinoma (OSCC) is a major cause of human mortality globally and radiotherapy is one of the main treatment modalities, however its therapeutic effect is often limited by radioresistance. JARID1B is an epigenetic factor with reported oncogenic potential in various cancer types. We investigated the effect of JARID1B inhibition on migration and invasion of human OSCC cell lines, as well as on clinical patients' outcome.
  
  
  METHODS
  Wound healing, matrigel invasion, Sulforhodamine B, and spheroid formation assays were used to characterize the signaling pathways of shJARID1B in response to radiation treatment. We evaluated the prognostic relevance of Jarid1b expression in a cohort of 81 OSCC patients.
  
  
  RESULTS
  Human OSCC cell lines, including SAS, HSC3, Cal27, TW2.6 and SCC4 cells, were used. shJARID1B cells significantly inhibited migration and invasion ability compared to their vector or wild type counterparts. Silencing shJARID1B significantly inhibited oral cancer stem cell activity and potentiated the tumor-inhibitory activity of radiation therapy in OSCC. Radiotherapy coupled with shJARID1B knockdown reduced mRNA levels of NQO1, KEAP1, NRF2, FOXO1, FOXO3, KLF4, OCT4, CD133, and Nanog in malignant OSCC cells. OSCC spheroid formation ability was markedly reduced in the shJARID1B cells. JARID1B overexpression is a dependent prognostic factor in OSCC patients.
  
  
  CONCLUSIONS
  Silencing shJARID1B inhibits migration and invasion of human OSCC, reduces cancer stem cell activities and potentiates tumor-inhibiting radiotherapeutic effects. JARID1B knockdown prior to radiotherapy is a potential effective therapeutic strategy for the treatment of OSCC.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Family Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan; Department of Occupational Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan; Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Bamodu Oluwaseun
authors.initials: BO
authors.lastname: Adebayo
authors.affiliation: The PhD Program of Translational Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defence Medical Center, Taipei, Taiwan.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defence Medical Centre, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Division of Histological and Clinical Pathology, Hualien Armed Forced General Hospital, Hualien, Taiwan.
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Wei-Hwa
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defence Medical Center, Taipei, Taiwan. Electronic address: j0607@ms6.hinet.net.
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Chao
authors.affiliation: Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan. Electronic address: ctyeh@s.tmu.edu.tw.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D034622:RNA Interference; D011836:Radiation Tolerance; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D013997:Time Factors; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D009687:Nuclear Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human
keywords: Cancer stem cell; Head and neck cancer; JARID1B; Oral cancer; Radiotherapy; shJARID1B