FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3082321333> ?p ?o ?g. }

• W3082321333 endingPage "497" @default.
• W3082321333 startingPage "469" @default.
• W3082321333 abstract "Background/aim Nearly all mammalian tumors of diverse tissues are believed to be dependent on fermentative glycolysis, marked by elevated production of lactic acid and expression of glycolytic enzymes, most notably lactic acid dehydrogenase (LDH). Therefore, there has been significant interest in developing chemotherapy drugs that selectively target various isoforms of the LDH enzyme. However, considerable questions remain as to the consequences of biological ablation of LDH or upstream targeting of the glycolytic pathway. Materials and methods In this study, we explore the biochemical and whole transcriptomic effects of CRISPR-Cas9 gene knockout (KO) of lactate dehydrogenases A and B [LDHA/B double KO (DKO)] and glucose-6-phosphate isomerase (GPI KO) in the human colon cancer cell line LS174T, using Affymetrix 2.1 ST arrays. Results The metabolic biochemical profiles corroborate that relative to wild type (WT), LDHA/B DKO produced no lactic acid, (GPI KO) produced minimal lactic acid and both KOs displayed higher mitochondrial respiration, and minimal use of glucose with no loss of cell viability. These findings show a high biochemical energy efficiency as measured by ATP in glycolysis-null cells. Next, transcriptomic analysis conducted on 48,226 mRNA transcripts reflect 273 differentially expressed genes (DEGS) in the GPI KO clone set, 193 DEGS in the LDHA/B DKO clone set with 47 DEGs common to both KO clones. Glycolytic-null cells reflect up-regulation in gene transcripts typically associated with nutrient deprivation / fasting and possible use of fats for energy: thioredoxin interacting protein (TXNIP), mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), PPARγ coactivator 1α (PGC-1α), and acetyl-CoA acyltransferase 2 (ACAA2). Other changes in non-ergometric transcripts in both KOs show losses in stemness, WNT signaling pathway, chemo/radiation resistance, retinoic acid synthesis, drug detoxification, androgen/estrogen activation, and extracellular matrix reprogramming genes. Conclusion These findings demonstrate that: 1) The Warburg effect is dispensable, 2) loss of the LDHAB gene is not only inconsequential to viability but fosters greater mitochondrial energy, and 3) drugs that target LDHA/B are likely to be ineffective without a plausible combination second drug target." @default.
• W3082321333 created "2020-09-08" @default.
• W3082321333 creator A5026912234 @default.
• W3082321333 creator A5035760747 @default.
• W3082321333 creator A5036681307 @default.
• W3082321333 creator A5050668551 @default.
• W3082321333 creator A5056430801 @default.
• W3082321333 creator A5061599283 @default.
• W3082321333 creator A5091254505 @default.
• W3082321333 date "2020-01-01" @default.
• W3082321333 modified "2023-10-18" @default.
• W3082321333 title "Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase" @default.
• W3082321333 cites W1490689662 @default.
• W3082321333 cites W1860523613 @default.
• W3082321333 cites W1878202475 @default.
• W3082321333 cites W1963788482 @default.
• W3082321333 cites W1969844814 @default.
• W3082321333 cites W1978348589 @default.
• W3082321333 cites W1981417481 @default.
• W3082321333 cites W1981451859 @default.
• W3082321333 cites W1985288999 @default.
• W3082321333 cites W1985786835 @default.
• W3082321333 cites W1986846962 @default.
• W3082321333 cites W1991429659 @default.
• W3082321333 cites W1993524465 @default.
• W3082321333 cites W2000467286 @default.
• W3082321333 cites W2004170579 @default.
• W3082321333 cites W2013430378 @default.
• W3082321333 cites W2013735638 @default.
• W3082321333 cites W2014251969 @default.
• W3082321333 cites W2020458598 @default.
• W3082321333 cites W2042421180 @default.
• W3082321333 cites W2045679421 @default.
• W3082321333 cites W2049202209 @default.
• W3082321333 cites W2054838472 @default.
• W3082321333 cites W2072645819 @default.
• W3082321333 cites W2087568713 @default.
• W3082321333 cites W2090388375 @default.
• W3082321333 cites W2112262745 @default.
• W3082321333 cites W2127603104 @default.
• W3082321333 cites W2133550391 @default.
• W3082321333 cites W2135914580 @default.
• W3082321333 cites W2139694192 @default.
• W3082321333 cites W2139718640 @default.
• W3082321333 cites W2141789735 @default.
• W3082321333 cites W2163995184 @default.
• W3082321333 cites W2170352988 @default.
• W3082321333 cites W2182878044 @default.
• W3082321333 cites W2208030089 @default.
• W3082321333 cites W2274302608 @default.
• W3082321333 cites W2291435605 @default.
• W3082321333 cites W2336181797 @default.
• W3082321333 cites W2408966316 @default.
• W3082321333 cites W2529349927 @default.
• W3082321333 cites W2531793316 @default.
• W3082321333 cites W2537623931 @default.
• W3082321333 cites W2546610174 @default.
• W3082321333 cites W2560159956 @default.
• W3082321333 cites W2562858475 @default.
• W3082321333 cites W2583332786 @default.
• W3082321333 cites W2585919199 @default.
• W3082321333 cites W2598400865 @default.
• W3082321333 cites W2602452026 @default.
• W3082321333 cites W2604837817 @default.
• W3082321333 cites W2608016504 @default.
• W3082321333 cites W2626027092 @default.
• W3082321333 cites W2734249847 @default.
• W3082321333 cites W2748978589 @default.
• W3082321333 cites W2752053733 @default.
• W3082321333 cites W2756405493 @default.
• W3082321333 cites W2767529657 @default.
• W3082321333 cites W2770171520 @default.
• W3082321333 cites W2777598902 @default.
• W3082321333 cites W2777685881 @default.
• W3082321333 cites W2791178771 @default.
• W3082321333 cites W2794078842 @default.
• W3082321333 cites W2796959290 @default.
• W3082321333 cites W2800088591 @default.
• W3082321333 cites W2800595297 @default.
• W3082321333 cites W2808996136 @default.
• W3082321333 cites W2855168245 @default.
• W3082321333 cites W2886597943 @default.
• W3082321333 cites W2889229834 @default.
• W3082321333 cites W2892772851 @default.
• W3082321333 cites W2895219712 @default.
• W3082321333 cites W2896965182 @default.
• W3082321333 cites W2898787300 @default.
• W3082321333 cites W2900569176 @default.
• W3082321333 cites W2900927838 @default.
• W3082321333 cites W2901157038 @default.
• W3082321333 cites W2901989248 @default.
• W3082321333 cites W2909429444 @default.
• W3082321333 cites W2911597143 @default.
• W3082321333 cites W2923596137 @default.
• W3082321333 cites W2924191132 @default.
• W3082321333 cites W2924349320 @default.
• W3082321333 cites W2929426408 @default.
• W3082321333 cites W2932691690 @default.

• next