title: Adenovirus-mediated RNA interference targeting FOXM1 transcription factor suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma.
abstract: BACKGROUND
  The Forkhead Box M1 (FOXM1) transcription factor, which regulates the expression of genes essential for cell proliferation and transformation, is implicated in tumorigenesis and tumor progression. FOXM1 has attracted much attention as a potential target for the prevention and/or therapeutic intervention in human carcinomas.
  
  
  METHODS
  The levels of FOXM1 expression in clinical tissue specimens and cell lines of human malignant nasopharyngeal carcinoma (NPC) were measured. Knockdown of FOXM1 expression was performed by small interfering RNA in NPC cells. An adenovirus vector (named AdFOXM1shRNA) was constructed to express a short hairpin RNA specific to FOXM1. The efficacy of AdFOXM1shRNA for tumor gene therapy in NPC cells and an in vivo NPC grafting model was assessed.
  
  
  RESULTS
  A strong expression of FOXM1 was observed in clinical tissue specimens and cell lines of human NPC. Knockdown of FOXM1 expression by FOXM1 specific small interfering RNA diminished the NPC cell proliferation. The infection of AdFOXM1shRNA in NPC cells resulted in the knockdown of FOXM1 mRNA and protein levels, correlated with the reduction of proliferation and anchorage-independent growth of the cancer cells. The growth of NPC tumors was significantly suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumor.
  
  
  CONCLUSIONS
  Together, our results suggest that FOXM1 is a potential therapeutic target for NPC and AdFOXM1shRNA may be an additional gene therapeutic intervention to be evaluated in future treatment strategies for patients with NPC.
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering