title: miR-574-5p negatively regulates Qki6/7 to impact β-catenin/Wnt signalling and the development of colorectal cancer.
abstract: OBJECTIVE
  Deficiency or reduced expression of signal transduction and activation of RNA family protein Quaking (Qki) is associated with developmental defects in neural and vascular tissues and the development of debilitating human diseases including colorectal cancer (CRC). However, the mechanisms underlying the aberrant downregulation or deficiency of Qki were uncertain.
  
  
  METHODS
  Expression of miR-574-5p, Qki5/6/7/7b splicing variants, β-catenin and p27(Kip1) was determined in mouse and human CRC cells and tissues to investigate the post-transcriptional regulation of Qki isoforms by miR-574-5p and its impact on β-catenin/p27(Kip1) signalling, cell cycle progression, proliferation, migration, invasion and tumour growth.
  
  
  RESULTS
  In the CRC tissues of C57BL/6-Apc(min/+) mice, miR-574-5p was found to be significantly upregulated and negatively correlated with the expression of Qki but positively correlated with the expression of β-catenin. In mouse and human CRC cells, miR-574-5p was shown to regulate Qki isoforms (Qki6/7 in particular) post-transcriptionally and caused altered expression in β-catenin and p27(Kip1) , increased proliferation, migration and invasion and decreased differentiation and cell cycle exit. Furthermore, in clinical CRC tissues, miR-574-5p was shown to be greatly upregulated and inversely correlated with the expression of Qkis. Finally, inhibition of miR-574-5p was shown to suppress the growth of tumours in the nude mice.
  
  
  CONCLUSIONS
  Together, these novel findings suggest that miR-574-5p is a potent ribo-regulator for Qkis and that aberrant miR-574-5p upregulation can be oncogenic.
authors.affiliation: State Key Laboratory of Cellular Stress Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Shunlong
authors.initials: S
authors.lastname: Ji
authors.forename: Gengtai
authors.initials: G
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Linpei
authors.initials: L
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Jianchun
authors.initials: J
authors.lastname: Cai
authors.forename: James Y
authors.initials: JY
authors.lastname: Yang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C558811:MIRN574 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C490832:QKI protein, human; D016601:RNA-Binding Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D050760:Cyclin-Dependent Kinase Inhibitor p27