Antisense Sp1 oligodeoxynucleotide decreases telomerase activity by inhibiting hTERT mRNA expression in Jurkat T

Jian-Xin Pang1, Xi-Yuan Cheng, Wei Xu

  • 1Institute of Pharmaceutic Sciences, First Military Medical University, Guangzhou 510515, China. pjx@fimmu.com

Abstract

Insights

Antisense Sp1 oligodeoxynucleotide (ODN) effectively reduces Sp1 expression in Jurkat T cells. This inhibition leads to decreased human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Telomerase plays a crucial role in cell immortality and is often upregulated in cancer.
  • Sp1 is a transcription factor that can regulate the expression of hTERT, a key component of telomerase.
  • Targeting Sp1 offers a potential strategy to inhibit telomerase activity.

Purpose of the Study:

  • To investigate the impact of Sp1 antisense oligodeoxynucleotide (ODN) on telomerase activity.
  • To examine the effect of Sp1 inhibition on human telomerase reverse transcriptase (hTERT) expression.

Main Methods:

  • Jurkat T cells were treated with Sp1 antisense ODN using lipofectamine.
  • Telomerase activity was measured using Telomerase PCR-ELISA.
  • Sp1 and hTERT mRNA levels were assessed by RT-PCR, and Sp1 protein levels by Western blot.

Main Results:

  • Sp1 antisense ODN significantly reduced Sp1 mRNA and protein levels in Jurkat T cells.
  • hTERT mRNA expression was suppressed by approximately 43.7% (P <0.01).
  • A dose-dependent inhibition of telomerase activity was observed, with reductions ranging from 27.1% to 64.6%.

Conclusions:

  • Antisense Sp1 ODN effectively inhibits Sp1 expression in Jurkat T cells.
  • The inhibition of Sp1 leads to decreased hTERT mRNA expression.
  • Sp1 antisense ODN reduces telomerase activity, suggesting a therapeutic target for cancers with high telomerase expression.

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