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000909166 1001_ $$00000-0002-8737-2610$$aBartl, Jasmin$$b0$$eCorresponding author
000909166 245__ $$aThe HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
000909166 260__ $$a[London]$$bNature Publishing Group UK$$c2022
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000909166 520__ $$aMost lncRNAs display species-specific expression patterns suggesting that animal models of cancer may only incompletely recapitulate the regulatory crosstalk between lncRNAs and oncogenic pathways in humans. Among these pathways, Sonic Hedgehog (SHH) signaling is aberrantly activated in several human cancer entities. We unravel that aberrant expression of the primate-specific lncRNA HedgeHog Interacting Protein-AntiSense 1 (HHIP-AS1) is a hallmark of SHH-driven tumors including medulloblastoma and atypical teratoid/rhabdoid tumors. HHIP-AS1 is actively transcribed from a bidirectional promoter shared with SHH regulator HHIP. Knockdown of HHIP-AS1 induces mitotic spindle deregulation impairing tumorigenicity in vitro and in vivo. Mechanistically, HHIP-AS1 binds directly to the mRNA of cytoplasmic dynein 1 intermediate chain 2 (DYNC1I2) and attenuates its degradation by hsa-miR-425-5p. We uncover that neither HHIP-AS1 nor the corresponding regulatory element in DYNC1I2 are evolutionary conserved in mice. Taken together, we discover an lncRNA-mediated mechanism that enables the pro-mitotic effects of SHH pathway activation in human tumors.
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000909166 7001_ $$0P:(DE-HGF)0$$aZanini, Marco$$b1
000909166 7001_ $$0P:(DE-HGF)0$$aBernardi, Flavia$$b2
000909166 7001_ $$0P:(DE-HGF)0$$aForget, Antoine$$b3
000909166 7001_ $$0P:(DE-HGF)0$$aBlümel, Lena$$b4
000909166 7001_ $$0P:(DE-HGF)0$$aTalbot, Julie$$b5
000909166 7001_ $$aPicard, Daniel$$b6
000909166 7001_ $$aQin, Nan$$b7
000909166 7001_ $$aCancila, Gabriele$$b8
000909166 7001_ $$aGao, Qingsong$$b9
000909166 7001_ $$aNath, Soumav$$b10
000909166 7001_ $$aKoumba, Idriss Mahoungou$$b11
000909166 7001_ $$aWolter, Marietta$$b12
000909166 7001_ $$aKuonen, François$$b13
000909166 7001_ $$00000-0001-8622-3261$$aLangini, Maike$$b14
000909166 7001_ $$aBeez, Thomas$$b15
000909166 7001_ $$aMunoz, Christopher$$b16
000909166 7001_ $$aPauck, David$$b17
000909166 7001_ $$aMarquardt, Viktoria$$b18
000909166 7001_ $$aYu, Hua$$b19
000909166 7001_ $$aSouphron, Judith$$b20
000909166 7001_ $$00000-0002-1721-7754$$aKorsch, Mascha$$b21
000909166 7001_ $$aMölders, Christina$$b22
000909166 7001_ $$aBerger, Daniel$$b23
000909166 7001_ $$aGöbbels, Sarah$$b24
000909166 7001_ $$aMeyer, Frauke-Dorothee$$b25
000909166 7001_ $$00000-0001-8316-6556$$aScheffler, Björn$$b26
000909166 7001_ $$aRotblat, Barak$$b27
000909166 7001_ $$00000-0001-7901-4752$$aDiederichs, Sven$$b28
000909166 7001_ $$00000-0002-6557-895X$$aRamaswamy, Vijay$$b29
000909166 7001_ $$00000-0002-8858-0294$$aSuzuki, Hiromishi$$b30
000909166 7001_ $$00000-0002-6261-138X$$aOro, Anthony$$b31
000909166 7001_ $$aStühler, Kai$$b32
000909166 7001_ $$aStefanski, Anja$$b33
000909166 7001_ $$00000-0002-2455-2489$$aFischer, Ute$$b34
000909166 7001_ $$aLeprivier, Gabriel$$b35
000909166 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b36
000909166 7001_ $$aSteger, Gerhard$$b37
000909166 7001_ $$00000-0003-1161-3622$$aBuell, Alexander$$b38
000909166 7001_ $$aKool, Marcel$$b39
000909166 7001_ $$aLichter, Peter$$b40
000909166 7001_ $$00000-0002-5447-5322$$aPfister, Stefan M.$$b41
000909166 7001_ $$00000-0002-1220-5252$$aNorthcott, Paul A.$$b42
000909166 7001_ $$00000-0001-7009-3466$$aTaylor, Michael D.$$b43
000909166 7001_ $$00000-0002-6121-4737$$aBorkhardt, Arndt$$b44
000909166 7001_ $$aReifenberger, Guido$$b45
000909166 7001_ $$00000-0002-7942-6674$$aAyrault, Olivier$$b46$$eCorresponding author
000909166 7001_ $$00000-0002-9404-9993$$aRemke, Marc$$b47$$eCorresponding author
000909166 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-022-31574-z$$gVol. 13, no. 1, p. 4061$$n1$$p4061$$tNature Communications$$v13$$x2041-1723$$y2022
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