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Your search keyword '"Langini, Maike"' showing total 3 results
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3 results on '"Langini, Maike"'

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

Author

Bartl J, Zanini M, Bernardi F, Forget A, Blümel L, Talbot J, Picard D, Qin N, Cancila G, Gao Q, Nath S, Koumba IM, 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 FD, 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 SM, Northcott PA, Taylor MD, Borkhardt A, Reifenberger G, Ayrault O, and Remke M

Subjects
Animals, Carrier Proteins metabolism, Cell Line, Tumor, Cell Proliferation, Dyneins metabolism, Gene Expression Regulation, Neoplastic, Hedgehog Proteins genetics, Hedgehog Proteins metabolism, Humans, Membrane Glycoproteins metabolism, Mice, Cerebellar Neoplasms genetics, Medulloblastoma genetics, MicroRNAs genetics, RNA, Long Noncoding genetics
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., (© 2022. The Author(s).)

Published
2022
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2. The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma.

Author

Ahmadov U, Picard D, Bartl J, Silginer M, Trajkovic-Arsic M, Qin N, Blümel L, Wolter M, Lim JKM, Pauck D, Winkelkotte AM, Melcher M, Langini M, Marquardt V, Sander F, Stefanski A, Steltgens S, Hassiepen C, Kaufhold A, Meyer FD, Seibt A, Kleinesudeik L, Hain A, Münk C, Knobbe-Thomsen CB, Schramm A, Fischer U, Leprivier G, Stühler K, Fulda S, Siveke JT, Distelmaier F, Borkhardt A, Weller M, Roth P, Reifenberger G, and Remke M

Subjects
Animals, Carcinogenesis genetics, Carcinogenesis pathology, Cell Line, Tumor, Cell Survival genetics, Clone Cells, Down-Regulation genetics, Gene Expression Regulation, Neoplastic, Glioblastoma pathology, Humans, Mice, Nude, MicroRNAs genetics, Mitochondria metabolism, Neoplasm Invasiveness, Phenotype, Prognosis, Protein Glutamine gamma Glutamyltransferase 2 metabolism, Proteogenomics, RNA, Small Interfering metabolism, Reactive Oxygen Species metabolism, Mice, Glioblastoma genetics, Glioblastoma radiotherapy, MicroRNAs metabolism, Radiation Tolerance genetics
Abstract

Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and MGMT promoter methylation status. Finally, the role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach., (© 2021. The Author(s).)

Published
2021
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3. The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma

Author

Ahmadov, Ulvi, Picard, Daniel, Bartl, Jasmin, Silginer, Manuela, Trajkovic-Arsic, Marija, Qin, Nan, Blümel, Lena, Wolter, Marietta, Lim, Jonathan K. M., Pauck, David, Winkelkotte, Alina M., Melcher, Marlen, Langini, Maike, Marquardt, Viktoria, Sander, Felix, Stefanski, Anja, Steltgens, Sascha, Hassiepen, Christina, Kaufhold, Anna, Meyer, Frauke-Dorothee, Seibt, Annette, Kleinesudeik, Lara, Hain, Anika, Münk, Carsten, Knobbe-Thomsen, Christiane Brigitte, Schramm, Alexander, Fischer, Ute, Leprivier, Gabriel, Stühler, Kai, Fulda, Simone, Siveke, Jens, Distelmaier, Felix, Borkhardt, Arndt, Weller, Michael, Roth, Patrick, Reifenberger, Guido, and Remke, Marc

Subjects
Proteomics, Carcinogenesis, Cell Survival, Medizin, Down-Regulation, Mice, Nude, Radiation Tolerance, Article, Cell Line, Tumor, Cancer genomics, Animals, Humans, Neoplasm Invasiveness, Protein Glutamine gamma Glutamyltransferase 2, ddc:610, RNA, Small Interfering, Transcriptomics, neoplasms, Proteogenomics, QH573-671, Prognosis, Clone Cells, Mitochondria, Gene Expression Regulation, Neoplastic, MicroRNAs, Phenotype, Long non-coding RNAs, Cytology, Glioblastoma, Reactive Oxygen Species
Abstract

Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and MGMT promoter methylation status. Finally, the role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.

Published
2020

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