title: Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition.
abstract: OBJECTIVE
  The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms.
  
  
  METHODS
  The expression dynamics of EIF5A2 were examined by immunohistochemistry in a cohort of carcinomatous and non-neoplastic colorectal tissues and cells. A series of in-vivo and in-vitro assays was performed to elucidate the function of EIF5A2 in CRC and its underlying mechanisms.
  
  
  RESULTS
  The overexpression of EIF5A2 was examined by immunohistochemistry in 102/229 (44.5%) CRC patients, and it was significantly correlated with tumour metastasis and determined to be an independent predictor of shortened survival (p<0.05). Ectopic overexpression of EIF5A2 in CRC cells enhanced cell motility and invasion in vitro and tumour metastasis in vivo, and induced epithelial-mesenchymal transition (EMT). The depletion of EIF5A2 expression prevented CRC cell invasiveness and inhibited EMT. Importantly, the metastasis-associated protein 1 (MTA1) gene was identified as a potential downstream target of EIF5A2 in CRC cells, and knockdown of MTA1 eliminated the augmentation of carcinoma cell migration, invasion and EMT by ectopic EIF5A2. The overexpression of EIF5A2 in CRC cells substantially enhanced the enrichment of c-myc on the promoter of MTA1, and MTA1 upregulation by EIF5A2 was partly dependent on c-myc.
  
  
  CONCLUSIONS
  The data suggest that EIF5A2 plays an important oncogenic role in CRC aggressiveness by the upregulation of MTA1 to induce EMT, and EIF5A2 could be employed as a novel prognostic marker and/or effective therapeutic target for CRC.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Tong
authors.forename: Sui-Sui
authors.initials: SS
authors.lastname: Dong
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Mai
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lin
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology; D009367:Neoplasm Staging; D010448:Peptide Initiation Factors / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000096:biosynthesis*; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000097574:Eukaryotic Translation Initiation Factor 5A; C116115:MYCBP protein, human; C089320:MTA1 protein, human