NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer - Aix-Marseille Université Access content directly
Journal Articles Nature Communications Year : 2018

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

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

Abstract

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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Human genetics
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Dates and versions

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

Identifiers

  • HAL Id : hal-01991348 , version 1

Cite

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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