title: Dysregulation of microRNA-34a expression in colorectal cancer inhibits the phosphorylation of FAK via VEGF.
abstract: BACKGROUND
  MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC).
  
  
  OBJECTIVE
  This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines.
  
  
  METHODS
  The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry.
  
  
  RESULTS
  MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment.
  
  
  CONCLUSIONS
  MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF.
authors.affiliation: Department of General Surgery, Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, 110001, China, 405538395@qq.com.
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010766:Phosphorylation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human