title: PAX6, a novel target of microRNA-7, promotes cellular proliferation and invasion in human colorectal cancer cells.
abstract: BACKGROUND
  Paired box 6 (PAX6), a highly conserved transcriptional factor, has been implicated in tumorigenesis.
  
  
  OBJECTIVE
  We aimed to explore the roles and molecular mechanisms of PAX6 and microRNA (miR-7) in colorectal cancer cells.
  
  
  METHODS
  Tissue microarray immunohistochemistry and Western blot were applied to examine the PAX6 expression. Real-time RT-PCR and Western blot were performed to determine the expression of miR-7 and PAX6. Luciferase reporter assay was used to determine whether PAX6 was a target of miR-7. Effects of miR-7 and PAX6 on colorectal cell proliferation, cell cycle progression, colony formation and invasion were then investigated. Western blot was used to determine the activities of the ERK and PI3K signal pathways, as well as the protein expression of MMP2 and MMP9.
  
  
  RESULTS
  The protein levels of PAX6 were gradually increased, while the expression of miR-7 was gradually reduced with malignancy of colorectal cancer. PAX6 was further identified as a target of miR-7, and its protein expression was negatively regulated by miR-7 in human colorectal cancer cells. Overexpression of PAX6 in Caco-2 and SW480 cells enhanced cellular proliferation, cell cycle progression, colony formation, and invasion, while miR-7 upregulation repressed these biological processes. Furthermore, the activities of ERK and PI3K signal pathways, as well as the protein levels of MMP2 and MMP9, were upregulated in PAX6-overexpressed Caco-2 and SW480 cells but deregulated in miR-7-overexpressed Caco-2 and SW480 cells.
  
  
  CONCLUSIONS
  Our study suggests that as a novel target of miR-7, PAX6 may serve as a promising therapeutic target for colorectal cancer.
authors.affiliation: Tumor Immunobiology Laboratory of Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Ministry of Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Li
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Li
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Pingli
authors.initials: P
authors.lastname: Xie
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Guancheng
authors.initials: G
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018938:Caco-2 Cells; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D005136:Eye Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; C549242:MIRN7-1 microRNA, human; C000605730:PAX6 protein, human