title: Knocking-down of CREPT prohibits the progression of oral squamous cell carcinoma and suppresses cyclin D1 and c-Myc expression.
abstract: BACKGROUND
  As a regulator essential for many cell cycle-related proteins, the robust expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT) implicates a poor diagnosis of endoderm and mesoderm-derived tumors. Whether CREPT plays the same role in the tumorigenesis derived from ectodermal tissues remains elusive.
  
  
  METHODS
  To explore the role of CREPT in ectoderm-derived tumors, cells from 7oral squamous cell carcinoma (OSCC) lines and 84clinical OSCC samples were exploited in this study. Quantitative PCR, Western blot assay and immunohistochemistry were applied in the evaluation of CREPT, cyclin D1 and c-Myc expression. Knocking-down of CREPT was performed by lentivirus delivering specific shRNA of CREPT. The effects of CREPT on OSCC were examined by cell proliferation, colony formation, apoptosis, cell migration and xenograft implantation experiments.
  
  
  RESULTS
  Compared with human normal oral keratinocytes, OSCC cell lines showed a significantly elevated expression of CREPT in both mRNA and protein levels. Consistently, samples from OSCC patients also exhibited a noticeably stronger CREPT expression than the noncancerous samples. In contrast, knocking down of CREPT in OSCC cell lines significantly reduced proliferation, colony formation and migration as well as the expression of cyclin D1 and c-Myc, but promoted apoptosis. Statistical analysis also suggested that CREPT expression was significantly correlated with the T and N classification of OSCC. Furthermore, CAL27 mouse xenograft model confirmed that down-regulation of CREPT prohibited cyclin D1 and c-Myc expression, through which decreased the in vivo tumor growth, but increased the survival ratio of hosts.
  
  
  CONCLUSIONS
  In OSCC cell lines, up-regulated CREPT expression enhanced cell proliferation, migration and cell cycle as well as promoted cyclin D1 and c-Myc expression as it did in endoderm and mesoderm-origin tumors. Our study strongly suggests that CREPT could be used as a marker for the OSCC prognosis and might work as a potential target in future OSCC therapy.
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.|Department of Stomatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Surgery, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiangpan
authors.initials: X
authors.lastname: Kong
authors.affiliation: School of Medicine, Nankai University, Tianjin, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Rongfa
authors.initials: R
authors.lastname: Bu
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C571225:RPRD1B protein, human; D019938:Cyclin D1