High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer

Int J Mol Sci. 2016 Jun 2;17(6):865. doi: 10.3390/ijms17060865.

Abstract

Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC.

Keywords: DNA repair; Let-7b; breast cancer; nucleotide excision repair pathway.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • DNA End-Joining Repair
  • DNA Repair*
  • Female
  • Gene Expression*
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • mirnlet7 microRNA, human