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

Details

Serval ID
serval:BIB_93213C10CC73
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors.
Journal
Nature communications
Author(s)
Bartl J., Zanini M., Bernardi F., Forget A., Blümel L., Talbot J., Picard D., Qin N., Cancila G., Gao Q., Nath S., Koumba I.M., Wolter M., Kuonen F., Langini M., Beez T., Munoz C., Pauck D., Marquardt V., Yu H., Souphron J., Korsch M., Mölders C., Berger D., Göbbels S., Meyer F.D., Scheffler B., Rotblat B., Diederichs S., Ramaswamy V., Suzuki H., Oro A., Stühler K., Stefanski A., Fischer U., Leprivier G., Willbold D., Steger G., Buell A., Kool M., Lichter P., Pfister S.M., Northcott P.A., Taylor M.D., Borkhardt A., Reifenberger G., Ayrault O., Remke M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
13/07/2022
Peer-reviewed
Oui
Volume
13
Number
1
Pages
4061
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Keywords
Animals, Carrier Proteins/metabolism, Cell Line, Tumor, Cell Proliferation, Cerebellar Neoplasms/genetics, Dyneins/metabolism, Gene Expression Regulation, Neoplastic, Hedgehog Proteins/genetics, Hedgehog Proteins/metabolism, Humans, Medulloblastoma/genetics, Membrane Glycoproteins/metabolism, Mice, MicroRNAs/genetics, RNA, Long Noncoding/genetics
Pubmed
Web of science
Open Access
Yes
Create date
25/07/2022 10:48
Last modification date
28/07/2022 6:36
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