title: Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker.
abstract: BACKGROUND
  Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways.
  
  
  METHODS
  We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case-control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n = 253) and a secondary cross-sectional cohort (over 65s; n = 649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender.
  
  
  CONCLUSIONS
  Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines.
  
  
  CONCLUSIONS
  This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia ; Food and Nutrition Flagship, CSIRO, North Ryde, NSW 2113, Australia.
authors.forename: Emma Louise
authors.initials: EL
authors.lastname: Beckett
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia.
authors.forename: Jeong Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Teaching and Research Unit, Central Coast Local Health District, PO Box 361, Gosford 2250, Australia.
authors.forename: Katrina
authors.initials: K
authors.lastname: King
authors.affiliation: Teaching and Research Unit, Central Coast Local Health District, PO Box 361, Gosford 2250, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Niblett
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia.
authors.forename: Lyndell
authors.initials: L
authors.lastname: Boyd
authors.affiliation: Food and Nutrition Flagship, CSIRO, North Ryde, NSW 2113, Australia.
authors.forename: Konsta
authors.initials: K
authors.lastname: Duesing
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Yates
authors.affiliation: Teaching and Research Unit, Central Coast Local Health District, PO Box 361, Gosford 2250, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Veysey
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Brush Rd, Ourimbah, NSW 2258, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
keywords: AP, Adenomatous polyps; Adenomatous polyps; CRC, Colorectal cancer; Colorectal cancer; Folate; MiR-21; MicroRNA