The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2022

The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors

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Jasmin Bartl
Flavia Bernardi
  • Function : Author
Antoine Forget
  • Function : Author
Lena Blümel
  • Function : Author
Julie Talbot
  • Function : Author
Daniel Picard
  • Function : Author
Nan Qin
  • Function : Author
Gabriele Cancila
  • Function : Author
Qingsong Gao
  • Function : Author
Soumav Nath
  • Function : Author
Idriss Mahoungou Koumba
  • Function : Author
Marietta Wolter
  • Function : Author
François Kuonen
  • Function : Author
Maike Langini
Thomas Beez
  • Function : Author
Christopher Munoz
  • Function : Author
David Pauck
  • Function : Author
Viktoria Marquardt
  • Function : Author
Hua Yu
  • Function : Author
Judith Souphron
  • Function : Author
Mascha Korsch
Christina Mölders
  • Function : Author
Daniel Berger
  • Function : Author
Sarah Göbbels
  • Function : Author
Frauke-Dorothee Meyer
  • Function : Author
Björn Scheffler
Barak Rotblat
  • Function : Author
Sven Diederichs
Vijay Ramaswamy
Hiromishi Suzuki
Anthony Oro
Kai Stühler
  • Function : Author
Anja Stefanski
  • Function : Author
Ute Fischer
Gabriel Leprivier
  • Function : Author
Dieter Willbold
  • Function : Author
Gerhard Steger
  • Function : Author
Alexander Buell
Marcel Kool
  • Function : Author
Peter Lichter
  • Function : Author
Stefan M Pfister
Paul A Northcott
Michael D Taylor
Arndt Borkhardt
Guido Reifenberger
  • Function : Author
Olivier Ayrault
Marc Remke

Abstract

Most lncRNAs display species-specific expression patterns suggesting that animal models of cancer may only incompletely recapitulate the regulatory crosstalk between lncRNAs and oncogenic pathways in humans. Among these pathways, Sonic Hedgehog (SHH) signaling is aberrantly activated in several human cancer entities. We unravel that aberrant expression of the primate-specific lncRNA HedgeHog Interacting Protein-AntiSense 1 (HHIP-AS1) is a hallmark of SHH-driven tumors including medulloblastoma and atypical teratoid/rhabdoid tumors. HHIP-AS1 is actively transcribed from a bidirectional promoter shared with SHH regulator HHIP. Knockdown of HHIP-AS1 induces mitotic spindle deregulation impairing tumorigenicity in vitro and in vivo. Mechanistically, HHIP-AS1 binds directly to the mRNA of cytoplasmic dynein 1 intermediate chain 2 (DYNC1I2) and attenuates its degradation by hsa-miR-425-5p. We uncover that neither HHIP-AS1 nor the corresponding regulatory element in DYNC1I2 are evolutionary conserved in mice. Taken together, we discover an lncRNA-mediated mechanism that enables the pro-mitotic effects of SHH pathway activation in human tumors.
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Dates and versions

hal-03862980 , version 1 (21-11-2022)

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Jasmin Bartl, Marco Zanini, Flavia Bernardi, Antoine Forget, Lena Blümel, et al.. The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors. Nature Communications, 2022, 13 (1), pp.4061. ⟨10.1038/s41467-022-31574-z⟩. ⟨hal-03862980⟩
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