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

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.

doi:10.1038/s41467-022-31574-z

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

Details

Download: 35831316_BIB_93213C10CC73.pdf (2807.80 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_93213C10CC73

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

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

Number

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

URN

urn:nbn:ch:serval-BIB_93213C10CC732

OAI-PMH

oai:serval.unil.ch:BIB_93213C10CC73

DOI

10.1038/s41467-022-31574-z

Pubmed

35831316

Web of science

000825090700001

Open Access

Yes