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Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells

Overview of attention for article published in BMC Genomic Data, December 2016
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Title
Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells
Published in
BMC Genomic Data, December 2016
DOI 10.1186/s12863-016-0459-1
Pubmed ID
Authors

Anna V. Kudryavtseva, Maria S. Fedorova, Alex Zhavoronkov, Alexey A. Moskalev, Alexander S. Zasedatelev, Alexey A. Dmitriev, Asiya F. Sadritdinova, Irina Y. Karpova, Kirill M. Nyushko, Dmitry V. Kalinin, Nadezhda N. Volchenko, Nataliya V. Melnikova, Kseniya M. Klimina, Dmitry V. Sidorov, Anatoly Y. Popov, Tatiana V. Nasedkina, Andrey D. Kaprin, Boris Y. Alekseev, George S. Krasnov, Anastasiya V. Snezhkina

Abstract

The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma. However, the mechanism of action of HKs in the promotion of tumor growth remains unclear. The purpose of the present study was to investigate the effect of silencing of hexokinase genes (HK1, HK2, and HK3) in colorectal cancer (HT-29, SW 480, HCT-15, RKO, and HCT 116) and melanoma (MDA-MB-435S and SK-MEL-28) cell lines using short hairpin RNA (shRNA) lentiviral vectors. shRNA lentiviral plasmid vectors pLSLP-HK1, pLSLP-HK2, and pLSLP-HK3 were constructed and then transfected separately or co-transfected into the cells. HK2 inactivation was associated with increased expression of HK1 in colorectal cancer cell lines pointing to the compensation effect. Simultaneous attenuation of HK1 and HK2 levels led to decreased cell viability. Co-transfection with shRNA vectors against HK1, HK2, and HK3 mRNAs resulted in a rapid cell death via apoptosis. We have demonstrated that simultaneous inactivation of HK1 and HK2 was sufficient to decrease proliferation and viability of melanoma and colorectal cancer cells. Our results suggest that HK1 and HK2 could be the key therapeutic targets for reducing aerobic glycolysis in examined cancers.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 18%
Student > Master 6 16%
Student > Bachelor 5 13%
Student > Ph. D. Student 3 8%
Student > Doctoral Student 2 5%
Other 5 13%
Unknown 10 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 29%
Agricultural and Biological Sciences 5 13%
Medicine and Dentistry 5 13%
Mathematics 1 3%
Immunology and Microbiology 1 3%
Other 3 8%
Unknown 12 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 24 December 2016.
All research outputs
#22,758,309
of 25,373,627 outputs
Outputs from BMC Genomic Data
#1,008
of 1,204 outputs
Outputs of similar age
#362,755
of 422,521 outputs
Outputs of similar age from BMC Genomic Data
#10
of 13 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,204 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 422,521 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.