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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastoma-initiating cells
|
|---|---|
| Published in |
Molecular Cancer, August 2015
|
| DOI | 10.1186/s12943-015-0432-z |
| Pubmed ID | |
| Authors |
Awais A. Mughal, Zanina Grieg, Håvard Skjellegrind, Artem Fayzullin, Mustapha Lamkhannat, Mrinal Joel, M. Shakil Ahmed, Wayne Murrell, Einar O. Vik-Mo, Iver A. Langmoen, Biljana Stangeland |
| Abstract |
Glioblastoma (GBM) is the most common primary brain malignancy and confers a dismal prognosis. GBMs harbor glioblastoma-initiating cells (GICs) that drive tumorigenesis and contribute to therapeutic resistance and tumor recurrence. Consequently, there is a strong rationale to target this cell population in order to develop new molecular therapies against GBM. Accumulating evidence indicates that Nα-terminal acetyltransferases (NATs), that are dysregulated in numerous human cancers, can serve as therapeutic targets. Microarrays were used to study the expression of several NATs including NAT12/NAA30 in clinical samples and stem cell cultures. The expression of NAT12/NAA30 was analyzed using qPCR, immunolabeling and western blot. We conducted shRNA-mediated knockdown of NAT12/NAA30 gene in GICs and studied the effects on cell viability, sphere-formation and hypoxia sensitivity. Intracranial transplantation to SCID mice enabled us to investigate the effects of NAT12/NAA30 depletion in vivo. Using microarrays we identified genes and biochemical pathways whose expression was altered upon NAT12/NAA30 down-regulation. While decreased expression of the distal 3'UTR of NAT12/NAA30 was generally observed in GICs and GBMs, this gene was strongly up-regulated at the protein level in GBM and GICs. The increased protein levels were not caused by increased levels of the steady state mRNA but rather by other mechanisms. Also, shorter 3'UTR of NAT12/NAA30 correlated with poor survival in glioma patients. As well, we observed previously not described nuclear localization of this typically cytoplasmic protein. When compared to non-silencing controls, cells featuring NAT12/NAA30 knockdown exhibited reduced cell viability, sphere-forming ability, and mitochondrial hypoxia tolerance. Intracranial transplantation showed that knockdown of NAT12/NAA30 resulted in prolonged animal survival. Microarray analysis of the knockdown cultures showed reduced levels of HIF1α and altered expression of several other genes involved in the hypoxia response. Furthermore, NAT12/NAA30 knockdown correlated with expressional dysregulation of genes involved in the p53 pathway, ribosomal assembly and cell proliferation. Western blot analysis revealed reduction of HIF1α, phospho-MTOR(Ser2448) and higher levels of p53 and GFAP in these cultures. NAT12/NAA30 plays an important role in growth and survival of GICs possibly by regulating hypoxia response (HIF1α), levels of p-MTOR (Ser2448) and the p53 pathway. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 6 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 50% |
| Science communicators (journalists, bloggers, editors) | 1 | 17% |
| Scientists | 1 | 17% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Norway | 1 | 2% |
| Unknown | 52 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 17% |
| Student > Master | 8 | 15% |
| Student > Ph. D. Student | 7 | 13% |
| Researcher | 6 | 11% |
| Student > Postgraduate | 4 | 8% |
| Other | 7 | 13% |
| Unknown | 12 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 23% |
| Medicine and Dentistry | 10 | 19% |
| Agricultural and Biological Sciences | 10 | 19% |
| Neuroscience | 2 | 4% |
| Computer Science | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 17 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 September 2015.
All research outputs
#13,211,650
of 22,824,164 outputs
Outputs from Molecular Cancer
#800
of 1,721 outputs
Outputs of similar age
#122,107
of 266,184 outputs
Outputs of similar age from Molecular Cancer
#16
of 46 outputs
Altmetric has tracked 22,824,164 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,721 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,184 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.