> Details

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 Marie; 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; [...]

The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma
  • Contributor: 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 Marie; 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; [...]
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: Cell Death & Disease
  • Language: English
  • DOI: 10.1038/s41419-021-04146-0
  • ISSN: 2041-4889
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>MGMT</jats:italic>) 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<jats:italic>HOXA</jats:italic>Transcript Antisense RNA, Myeloid-Specific 1 (<jats:italic>HOTAIRM1</jats:italic>) was determined by analyzing<jats:italic>HOTAIRM1</jats:italic>in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and<jats:italic>MGMT</jats:italic>promoter methylation status. Finally, the role of<jats:italic>HOTAIRM1</jats:italic>in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified<jats:italic>HOTAIRM1</jats:italic>as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and<jats:italic>MGMT</jats:italic>promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon<jats:italic>HOTAIRM1</jats:italic>down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon<jats:italic>HOTAIRM1</jats:italic>knock-down.<jats:italic>HOTAIRM1</jats:italic>knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of<jats:italic>TGM2</jats:italic>mimicked the phenotype of<jats:italic>HOTAIRM1</jats:italic>down-regulation in glioblastoma cells. Moreover,<jats:italic>HOTAIRM1</jats:italic>modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for<jats:italic>HOTAIRM1</jats:italic>as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting<jats:italic>HOTAIRM1</jats:italic>may be a promising new therapeutic approach.</jats:p>
  • Access State: Open Access