title: The miR-196b miRNA inhibits the GATA6 intestinal transcription factor and is upregulated in colon cancer patients.
abstract: OBJECTIVE
  To explore the possible misexpression of the microRNA miR-196b in colorectal cancer (CRC) and its role in controlling the expression of GATA6, a putative target gene crucial to intestinal cell homeostasis and tumorigenesis.
  
  
  METHODS
  The expression of miR-196b was analysed by qRT-PCR in surgical resection samples from a cohort of sporadic colon cancer patients. Manipulations of miR-196b expression were performed to demonstrate its inhibition of GATA6 protein levels.
  
  
  RESULTS
  We found that miR-196b is significantly upregulated in pre-treatment surgical resection samples from a cohort of sporadic colon cancer patients. The upregulation of miR-196b correlates with less severe clinicopathological characteristics, such as early tumor stage and absence of lymph node metastases. We show that in CRC cells, miR-196b targets the mRNA of GATA6, a transcription factor involved in the homeostasis and differentiation of intestinal epithelial cells, and a positive regulator of the Wnt/β-catenin pathway. We moreover found that the increase of miR-196b correlates with a reduced GATA6 protein expression in colon cancer patients.
  
  
  CONCLUSIONS
  Our results establish miR-196b as a post-transcriptional inhibitor of GATA6 in CRC cells, implicating miR-196b function in gene regulatory pathways crucial to intestinal cell homeostasis and tumorigenesis. Our results furthermore suggest a role of miR-196b expression in CRC, as an antagonist of GATA6 function in tumor cells, thus providing the basis for a potential targeting strategy for the treatment of CRC.
authors.affiliation: Department of Life Sciences, Modena 41125, Italy.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fantini
authors.affiliation: Department of Life Sciences, Modena 41125, Italy.|Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, University of Modena and Reggio Emilia, Modena 41125, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salsi
authors.affiliation: Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica, University of Modena and Reggio Emilia, Modena 41124, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Reggiani
authors.affiliation: Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica, University of Modena and Reggio Emilia, Modena 41124, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Maiorana
authors.affiliation: Department of Life Sciences, Modena 41125, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Zappavigna
mesh_terms: D020413:3' Untranslated Regions; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: colorectal cancer; gene expression; gene regulation; molecular carcinogenesis; molecular mechanisms