TY  - JOUR
AU  - Bartl, Jasmin
AU  - Zanini, Marco
AU  - Bernardi, Flavia
AU  - Forget, Antoine
AU  - Blümel, Lena
AU  - Talbot, Julie
AU  - Picard, Daniel
AU  - Qin, Nan
AU  - Cancila, Gabriele
AU  - Gao, Qingsong
AU  - Nath, Soumav
AU  - Koumba, Idriss Mahoungou
AU  - Wolter, Marietta
AU  - Kuonen, François
AU  - Langini, Maike
AU  - Beez, Thomas
AU  - Munoz, Christopher
AU  - Pauck, David
AU  - Marquardt, Viktoria
AU  - Yu, Hua
AU  - Souphron, Judith
AU  - Korsch, Mascha
AU  - Mölders, Christina
AU  - Berger, Daniel
AU  - Göbbels, Sarah
AU  - Meyer, Frauke-Dorothee
AU  - Scheffler, Björn
AU  - Rotblat, Barak
AU  - Diederichs, Sven
AU  - Ramaswamy, Vijay
AU  - Suzuki, Hiromishi
AU  - Oro, Anthony
AU  - Stühler, Kai
AU  - Stefanski, Anja
AU  - Fischer, Ute
AU  - Leprivier, Gabriel
AU  - Willbold, Dieter
AU  - Steger, Gerhard
AU  - Buell, Alexander
AU  - Kool, Marcel
AU  - Lichter, Peter
AU  - Pfister, Stefan
AU  - Northcott, Paul A
AU  - Taylor, Michael D
AU  - Borkhardt, Arndt
AU  - Reifenberger, Guido
AU  - Ayrault, Olivier
AU  - Remke, Marc
TI  - The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2022-01467
SP  - 4061
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35831316
DO  - DOI:10.1038/s41467-022-31574-z
UR  - https://inrepo02.dkfz.de/record/180667
ER  -