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The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
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 huma...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279496/ https://www.ncbi.nlm.nih.gov/pubmed/35831316 http://dx.doi.org/10.1038/s41467-022-31574-z |
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| author | Bartl, Jasmin Zanini, Marco Bernardi, Flavia Forget, Antoine Blümel, Lena Talbot, Julie Picard, Daniel Qin, Nan Cancila, Gabriele Gao, Qingsong Nath, Soumav Koumba, Idriss Mahoungou Wolter, Marietta Kuonen, François Langini, Maike Beez, Thomas Munoz, Christopher Pauck, David Marquardt, Viktoria Yu, Hua Souphron, Judith Korsch, Mascha Mölders, Christina Berger, Daniel Göbbels, Sarah Meyer, Frauke-Dorothee Scheffler, Björn Rotblat, Barak Diederichs, Sven Ramaswamy, Vijay Suzuki, Hiromishi Oro, Anthony Stühler, Kai Stefanski, Anja Fischer, Ute Leprivier, Gabriel Willbold, Dieter Steger, Gerhard Buell, Alexander Kool, Marcel Lichter, Peter Pfister, Stefan M. Northcott, Paul A. Taylor, Michael D. Borkhardt, Arndt Reifenberger, Guido Ayrault, Olivier Remke, Marc |
| author_facet | Bartl, Jasmin Zanini, Marco Bernardi, Flavia Forget, Antoine Blümel, Lena Talbot, Julie Picard, Daniel Qin, Nan Cancila, Gabriele Gao, Qingsong Nath, Soumav Koumba, Idriss Mahoungou Wolter, Marietta Kuonen, François Langini, Maike Beez, Thomas Munoz, Christopher Pauck, David Marquardt, Viktoria Yu, Hua Souphron, Judith Korsch, Mascha Mölders, Christina Berger, Daniel Göbbels, Sarah Meyer, Frauke-Dorothee Scheffler, Björn Rotblat, Barak Diederichs, Sven Ramaswamy, Vijay Suzuki, Hiromishi Oro, Anthony Stühler, Kai Stefanski, Anja Fischer, Ute Leprivier, Gabriel Willbold, Dieter Steger, Gerhard Buell, Alexander Kool, Marcel Lichter, Peter Pfister, Stefan M. Northcott, Paul A. Taylor, Michael D. Borkhardt, Arndt Reifenberger, Guido Ayrault, Olivier Remke, Marc |
| author_sort | Bartl, Jasmin |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-9279496 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-92794962022-07-15 The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors Bartl, Jasmin Zanini, Marco Bernardi, Flavia Forget, Antoine Blümel, Lena Talbot, Julie Picard, Daniel Qin, Nan Cancila, Gabriele Gao, Qingsong Nath, Soumav Koumba, Idriss Mahoungou Wolter, Marietta Kuonen, François Langini, Maike Beez, Thomas Munoz, Christopher Pauck, David Marquardt, Viktoria Yu, Hua Souphron, Judith Korsch, Mascha Mölders, Christina Berger, Daniel Göbbels, Sarah Meyer, Frauke-Dorothee Scheffler, Björn Rotblat, Barak Diederichs, Sven Ramaswamy, Vijay Suzuki, Hiromishi Oro, Anthony Stühler, Kai Stefanski, Anja Fischer, Ute Leprivier, Gabriel Willbold, Dieter Steger, Gerhard Buell, Alexander Kool, Marcel Lichter, Peter Pfister, Stefan M. Northcott, Paul A. Taylor, Michael D. Borkhardt, Arndt Reifenberger, Guido Ayrault, Olivier Remke, Marc Nat Commun Article 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. Nature Publishing Group UK 2022-07-13 /pmc/articles/PMC9279496/ /pubmed/35831316 http://dx.doi.org/10.1038/s41467-022-31574-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Bartl, Jasmin Zanini, Marco Bernardi, Flavia Forget, Antoine Blümel, Lena Talbot, Julie Picard, Daniel Qin, Nan Cancila, Gabriele Gao, Qingsong Nath, Soumav Koumba, Idriss Mahoungou Wolter, Marietta Kuonen, François Langini, Maike Beez, Thomas Munoz, Christopher Pauck, David Marquardt, Viktoria Yu, Hua Souphron, Judith Korsch, Mascha Mölders, Christina Berger, Daniel Göbbels, Sarah Meyer, Frauke-Dorothee Scheffler, Björn Rotblat, Barak Diederichs, Sven Ramaswamy, Vijay Suzuki, Hiromishi Oro, Anthony Stühler, Kai Stefanski, Anja Fischer, Ute Leprivier, Gabriel Willbold, Dieter Steger, Gerhard Buell, Alexander Kool, Marcel Lichter, Peter Pfister, Stefan M. Northcott, Paul A. Taylor, Michael D. Borkhardt, Arndt Reifenberger, Guido Ayrault, Olivier Remke, Marc The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title | The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title_full | The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title_fullStr | The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title_full_unstemmed | The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title_short | The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors |
| title_sort | hhip-as1 lncrna promotes tumorigenicity through stabilization of dynein complex 1 in human shh-driven tumors |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279496/ https://www.ncbi.nlm.nih.gov/pubmed/35831316 http://dx.doi.org/10.1038/s41467-022-31574-z |
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