PXD020141

PXD020141 is an original dataset announced via ProteomeXchange.

Title	The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma
Description	Glioblastoma is the most common malignant primary brain tumor. Clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNA (lncRNA) alterations may contribute to glioblastoma pathogenesis and potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was analyzed in multiple glioblastoma gene expression data sets for associations with prognosis and IDH mutation and MGMT promoter methylation status. 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, less invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses and determination of reactive oxygen species (ROS) levels revealed impaired mitochondrial function and increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2) as 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 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.
HostingRepository	PRIDE
AnnounceDate	2022-01-19
AnnouncementXML	Submission_2022-01-19_03:09:01.340.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anja Stefanski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-01 08:53:24	ID requested
⏵ 1	2022-01-19 03:09:02	announced

Ahmadov U, Picard D, Bartl J, Silginer M, Trajkovic-Arsic M, Qin N, Bl, ü, mel 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, M, ü, nk C, Knobbe-Thomsen CB, Schramm A, Fischer U, Leprivier G, St, ü, hler K, Fulda S, Siveke JT, Distelmaier F, Borkhardt A, Weller M, Roth P, Reifenberger G, Remke M, The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma. Cell Death Dis, 12(10):885(2021) [pubmed]

submitter keyword: Glioblastoma

HOTAIRM1

long non-coding RNA

radiosensitivity

Kai Stühler
contact affiliation	Institute for Molecular Medicine I Medical Faculty Heinrich-Heine-University Duesseldorf Universitaetsstrasse 1 40225 Duesseldorf Germany
contact email	kai.stuehler@hhu.de
lab head
Anja Stefanski
contact affiliation	Molecular Proteomics Laboratory
contact email	anja.stefanski@hhu.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/01/PXD020141

PRIDE project URI

• PRIDE
  1. PXD020141
     1. Label: PRIDE project
     2. Name: The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma