title: MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts.
abstract: METHODS
  MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients.
  
  
  RESULTS
  We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes.
  
  
  CONCLUSIONS
  PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research.
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Nuñez-Sánchez
authors.affiliation: Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Dávalos
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.affiliation: Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casas-Agustench
authors.affiliation: Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, Madrid, Spain.
authors.forename: Francesco
authors.initials: F
authors.lastname: Visioli
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.|Nutrition Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Monedero-Saiz
authors.affiliation: Nutrition Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Noelia V
authors.initials: NV
authors.lastname: García-Talavera
authors.affiliation: Nutrition Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: María B
authors.initials: MB
authors.lastname: Gómez-Sánchez
authors.affiliation: Nutrition Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Álvarez
authors.affiliation: Digestive Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: García-Albert
authors.affiliation: Digestive Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rodríguez-Gil
authors.affiliation: Surgery Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Marín
authors.affiliation: Anatomical Pathology Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Pastor-Quirante
authors.affiliation: Anatomical Pathology Service, Hospital Reina Sofía, Avda. Intendente Jorge Palacios s/n, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Díaz
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Conesa
authors.affiliation: Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D003106:Colon / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D029561:Lythraceae; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology*; D011300:Preoperative Care
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D010936:Plant Extracts
keywords: Clinical trials; Colon cancer; Pomegranate; Urolithins; microRNA