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Genetic regulation of TERT splicing contributes to reduced or elevated cancer risk by altering cellular longevity and replicative potential — Europe PMC PPR:PPR935997

Source: Europe PMC
Original: https://europepmc.org/article/PPR/PPR935997
DOI: 10.1101/2024.11.04.24316722
License (as archived): CC0-1.0
Archived: 2026-10-06T15:12:39.454Z
SHA-256 of the archived text: 43f61f3d61a93b394a87906e5f2f7e916bf1726ce20d5374f69bb5279e639d23
Stable URL of this page: https://metraipolis.com/documento/dc_5d760c926feb

How to cite

Genetic regulation of TERT splicing contributes to reduced or elevated cancer risk by altering cellular longevity and replicative potential — Europe PMC PPR:PPR935997 — Europe PMC, https://europepmc.org/article/PPR/PPR935997 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_5d760c926feb (Metraipolis archive dc_5d760c926feb, sha256 43f61f3d61a93b394a87906e5f2f7e916bf1726ce20d5374f69bb5279e639d23)

BibTeX

@misc{dc5d760c926feb,
  title = {Genetic regulation of TERT splicing contributes to reduced or elevated cancer risk by altering cellular longevity and replicative potential — Europe PMC PPR:PPR935997},
  howpublished = {Europe PMC},
  url = {https://europepmc.org/article/PPR/PPR935997},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_5d760c926feb; sha256 43f61f3d61a93b394a87906e5f2f7e916bf1726ce20d5374f69bb5279e639d23},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC, https://europepmc.org/article/PPR/PPR935997. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

ABSTRACT: The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within TERT intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.5-66.5 repeats) and GWAS signals within TERT intron 4. Specifically, VNTR6-1 fully explained the GWAS signals for rs2242652 and partially for rs10069690. VNTR6-1, rs10069690 and their haplotypes were associated with multi-cancer risk and age-related telomere shortening. Both variants reduce TERT expression through alternative splicing and nonsense-mediated decay: rs10069690-T increases intron 4 retention and VNTR6-1-Long expands a polymorphic G quadruplex (G4, 35-113 copies) within intron 6. Treatment with G4-stabilizing ligands decreased the fraction of the functional telomerase-encoding TERT full-length isoform, whereas CRISPR/Cas9 deletion of VNTR6-1 increased this fraction and apoptosis while reducing cell proliferation. Thus, VNTR6-1 and rs10069690 regulate the expression and splicing of TERT transcripts encoding both functional and nonfunctional telomerase. Altered TERT isoform ratios might modulate cellular longevity and replicative potential at homeostasis and in response to environmental factors, thus selectively contributing to the reduced or elevated cancer risk conferred by this locus.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: medRxiv, 2024 (prima pubblicazione 2024-11-05).
Identificativi: DOI 10.1101/2024.11.04.24316722.
Pagina: https://europepmc.org/article/PPR/PPR935997 — https://doi.org/10.1101/2024.11.04.24316722. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-10-06T15:11:36.240Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.