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Updated: Jul 26, 2025

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

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Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be

Aamir Amin1, Marzia Morello2, Maria Raffaella Petrara1

  • 1Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy.

Cancers
|June 22, 2023
PubMed

Insights

Short-term inhibition of telomerase reverse transcriptase (TERT) impairs cancer cell growth by reducing MYC levels via NF-κB signaling. This strategy, combined with chemotherapy, shows promise for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Telomerase reverse transcriptase (TERT) is implicated in carcinogenesis through mechanisms beyond telomere length.
  • Previous studies showed short-term TERT inhibition by BIBR1532 impairs cell proliferation without affecting telomere length.

Purpose of the Study:

  • To investigate the cell cycle effects of short-term TERT inhibition in B-cell malignancies.
  • To elucidate the molecular mechanisms underlying TERT inhibition-induced cell cycle arrest.
  • To evaluate the efficacy of TERT inhibition in combination with antineoplastic drugs.

Main Methods:

  • In vitro studies using EBV-immortalized LCLs and Burkitt's lymphoma cell lines.
  • Analysis of NF-κB p65, MYC, and P21 expression and localization.
  • In vivo studies using wild-type zebrafish embryos and a zebrafish xenograft model.
  • Combination therapy with BIBR1532 and cyclophosphamide or fludarabine.

Main Results:

  • Short-term TERT inhibition reduced NF-κB p65 nuclear levels, leading to MYC downregulation.
  • MYC downregulation correlated with increased P21 expression and nuclear localization, promoting cell cycle inhibition.
  • BIBR1532 treatment decreased Myc and increased p21 expression in zebrafish embryos.
  • Combination therapy significantly reduced xenografted cell proliferation compared to monotherapy.

Conclusions:

  • Short-term TERT inhibition impairs cancer cell growth by downregulating MYC through NF-κB signaling.
  • TERT inhibitors combined with antineoplastic drugs represent a potential anticancer strategy.
Keywords:
EBV-immortalized and fully transformed B cellsMYCNF-kB p65TERT extra-telomeric functionsTERT/telomerasenew therapeutic approachxenograftzebrafish

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