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Inhibition of TF gene expression by antisense oligonucleotides in different cancer cell lines

Yvonne Förster1, Bernd Schwenzer

  • 1Institute of Biochemistry, Technical University Dresden, Germany.

Journal of Experimental Therapeutics & Oncology
|April 23, 2005
PubMed

Insights

Antisense oligonucleotides (AS-ODNs) targeting human tissue factor (TF) mRNA effectively inhibited TF gene expression in various cancer cell lines. Optimal AS-ODN efficacy was linked to their location within the translated region of TF mRNA.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Oncology

Background:

  • Human tissue factor (TF) initiates blood coagulation and plays a role in tumor angiogenesis and metastasis.
  • Antisense oligonucleotides (AS-ODNs) offer a potential therapeutic strategy by inhibiting gene expression.

Purpose of the Study:

  • To evaluate the efficiency of computationally predicted AS-ODNs against human TF mRNA.
  • To identify optimal AS-ODN sequences and target regions for TF gene inhibition.

Main Methods:

  • Computational prediction of TF mRNA structure to select AS-ODNs.
  • Testing fourteen different AS-ODNs in three cancer cell lines (MCF-7, T508, J82).
  • Assessing TF gene and protein expression inhibition levels.

Main Results:

  • AS-ODN AS-7 inhibited TF gene expression by up to 50% in MCF-7 cells.
  • Further optimized AS-ODNs showed enhanced inhibition.
  • TF gene expression was inhibited by 30% in T508 cells (AS-4), and TF protein by 68% in J82 cells (two AS-ODNs).
  • Effective AS-ODNs were consistently located in the translated region of TF mRNA.

Conclusions:

  • AS-ODNs targeting the translated region of TF mRNA are effective in inhibiting TF gene expression across different cancer cell lines.
  • AS-ODN efficacy is relatively independent of the cell line, but optimal transfection conditions are cell-line specific.

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