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Inhibition of telomerase activity by HDV ribozyme in cancers

Yingying Lu1, Junchao Gu, Dachuan Jin

  • 1Department of Medicine, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing 100050, PR China. ham69@sina.com

Journal of Experimental & Clinical Cancer Research : CR
|January 7, 2011
PubMed
Abstract

Insights

A novel HDV ribozyme effectively targets human telomerase RNA (hTR), inhibiting cancer cell proliferation and inducing apoptosis. This ribozyme represents a promising strategy for anti-cancer gene therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Therapy

Background:

  • Telomerase is crucial for cell proliferation and cancer development.
  • Targeting telomerase offers a potential anti-cancer drug strategy.
  • Inhibiting telomerase RNA's template function can reduce its activity.

Purpose of the Study:

  • To design and synthesize a pseudo-knotted HDV ribozyme (g.RZ57) targeting the human telomerase RNA (hTR).
  • To evaluate the ribozyme's efficacy in cleaving hTR both in vitro and in vivo.
  • To assess the impact of ribozyme activity on cancer cell proliferation and telomerase levels.

Main Methods:

  • Designed and synthesized a pseudo-knotted HDV ribozyme (g.RZ57) against hTR.
  • Constructed in vitro transcription and eukaryotic expression plasmids for the ribozyme.
  • Transfected the ribozyme into hepatocellular carcinoma (7402), colon cancer (HCT116) cells, and L02 hepatocytes.

Main Results:

  • The HDV ribozyme demonstrated specific in vitro cleavage of hTR, achieving up to 70.4% cleavage.
  • Transfection into cancer cells induced growth arrest and spontaneous apoptosis.
  • Telomerase activity in transfected cells decreased to 10% of pre-transfection levels.

Conclusions:

  • The HDV ribozyme (g.RZ57) effectively cleaves human telomerase RNA.
  • This ribozyme shows significant potential as an anti-cancer gene therapy agent.
  • The study validates HDV ribozyme as an effective strategy for cancer treatment.

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