Noncanonical functions of telomerase and telomeres in viruses-associated cancer

J Med Virol. 2024 May;96(5):e29665. doi: 10.1002/jmv.29665.

Abstract

The cause of cancer is attributed to the uncontrolled growth and proliferation of cells resulting from genetic changes and alterations in cell behavior, a phenomenon known as epigenetics. Telomeres, protective caps on the ends of chromosomes, regulate both cellular aging and cancer formation. In most cancers, telomerase is upregulated, with the telomerase reverse transcriptase (TERT) enzyme and telomerase RNA component (TERC) RNA element contributing to the maintenance of telomere length. Additionally, it is noteworthy that two viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), utilize telomerase for their replication or persistence in infected cells. Also, TERT and TERC may play major roles in cancer not related to telomere biology. They are involved in the regulation of gene expression, signal transduction pathways, cellular metabolism, or even immune response modulation. Furthermore, the crosstalk between TERT, TERC, RNA-binding proteins, and microRNAs contributes to a greater extent to cancer biology. To understand the multifaceted roles played by TERT and TERC in cancer and viral life cycles, and then to develop effective therapeutic strategies against these diseases, are fundamental for this goal. By investigating deeply, the complicated mechanisms and relationships between TERT and TERC, scientists will open the doors to new therapies. In its analysis, the review emphasizes the significance of gaining insight into the multifaceted roles that TERT and TERC play in cancer pathogenesis, as well as their involvement in the viral life cycle for designing effective anticancer therapy approaches.

Keywords: EBV; HPV; TERC; hTERT; human cancer; oncogenic viruses; telomerase.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / pathogenicity
  • Herpesvirus 4, Human / physiology
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / virology
  • RNA / genetics
  • RNA / metabolism
  • Telomerase* / genetics
  • Telomerase* / metabolism
  • Telomere* / metabolism

Substances

  • Telomerase
  • telomerase RNA
  • RNA
  • TERT protein, human