Detection of mRNA of the cyclin D1 breast cancer marker by a novel duplex-DNA probe

J Med Chem. 2013 Jun 27;56(12):4860-9. doi: 10.1021/jm301838y. Epub 2013 Jun 6.

Abstract

Previously, we have described 5-((4-methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6, as a fluorescent uridine analogue exhibiting a 3000-fold higher quantum yield (Φ 0.12) and maximum emission (478 nm) which is 170 nm red-shifted as compared to uridine. Here, we utilized 6 for preparation of labeled oligodeoxynucleotide (ODN) probes based on MS2 and cyclin D1 (a known breast cancer mRNA marker) sequences. Cyclin D1-derived labeled-ssODN showed a 9.5-fold decrease of quantum yield upon duplex formation. On the basis of this finding, we developed the ds-NIF (nucleoside with intrinsic fluorescence)-probe methodology for detection of cyclin D1 mRNA, by which the fluorescent probe is released upon recognition of target mRNA by the relatively dark NIF-duplex-probe. Indeed, we successfully detected, a ss-deoxynucleic acid (DNA) variant of cyclin D1 mRNA using a dark NIF-labeled duplex-probe, and monitoring the recognition process by fluorescence spectroscopy and gel electrophoresis. Furthermore, we successfully detected cyclin D1 mRNA in RNA extracted from cancerous human cells, using ds-NIF methodology.

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism*
  • DNA Probes / genetics
  • DNA Probes / metabolism*
  • Humans
  • Molecular Probe Techniques*
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spectrometry, Fluorescence
  • Temperature

Substances

  • Biomarkers, Tumor
  • DNA Probes
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Cyclin D1