NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2018

NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer

Andrew T. Ludlow
  • Fonction : Auteur
Mandy Sze Wong
  • Fonction : Auteur
Kimberly Batten
  • Fonction : Auteur
Laura Yuan
  • Fonction : Auteur
Tsung-Po Lai
  • Fonction : Auteur
Nicole Dahlson
  • Fonction : Auteur
Lu Zhang
  • Fonction : Auteur
  • PersonId : 764723
  • IdRef : 200027433
Ilgen Mender
  • Fonction : Auteur
Enzo Tedone
  • Fonction : Auteur
Mohammed E. Sayed
  • Fonction : Auteur
Woodring E. Wright
  • Fonction : Auteur
Jerry W. Shay
  • Fonction : Auteur

Résumé

Alternative splicing is dysregulated in cancer and the reactivation of telomerase involves the splicing of TERT transcripts to produce full-length (FL) TERT. Knowledge about the splicing factors that enhance or silence FL hTERT is lacking. We identified splicing factors that reduced telomerase activity and shortened telomeres using a siRNA minigene reporter screen and a lung cancer cell bioinformatics approach. A lead candidate, NOVA1, when knocked down resulted in a shift in hTERT splicing to non-catalytic isoforms, reduced telomerase activity, and progressive telomere shortening. NOVA1 knockdown also significantly altered cancer cell growth in vitro and in xenografts. Genome engineering experiments reveal that NOVA1 promotes the inclusion of exons in the reverse transcriptase domain of hTERT resulting in the production of FL hTERT transcripts. Utilizing hTERT splicing as a model splicing event in cancer may provide new insights into potentially targetable dysregulated splicing factors in cancer.
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Dates et versions

hal-01991348 , version 1 (23-01-2019)

Identifiants

  • HAL Id : hal-01991348 , version 1

Citer

Andrew T. Ludlow, Mandy Sze Wong, Jérôme Robin-Ducellier, Kimberly Batten, Laura Yuan, et al.. NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer. Nature Communications, 2018, 9. ⟨hal-01991348⟩

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