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Results for “glycolysis”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Notch signaling regulates the expression of glycolysis-related genes in a context-dependent manner during embryonic development

Highlights: • Notch does not regulate glycolysis genes during early embryonic development. • Notch regulates glycolysis genes differently in the brain at the larval stage. • Notch-mediated glycolysis gene regulation is context-dependent during development. Glycolysis, the classic pathway for producing energy, has been known to be involved in neural development. Notch signaling also contributes to neural development and regulation of glycolysis in various tissues. However, the role of Notch signaling in glycolysis-related gene regulation during neural development is poorly understood. Here, we analyzed mRNA expression patterns and levels of glucose transporters (GLUT) as well as rate-limiting enzymes in glycolysis using zebrafish mib1{sup ta52b} mutants, in which Notch signaling was deficient at the early embryonic and larval stages. Our results indicated that in neural tissues, Notch signaling positively regulates glut1a and glut3a expression and negatively regulates hk2 expression at the larval stage but may not regulate them during early embryonic stages. Therefore, these results suggest that Notch signaling regulates glycolysis-related gene expression in a context-dependent manner in neural tissues at different developmental stages.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Novel insight into the kinetics of amide bond glycolysis for nylon-6 depolymerization

Chemical recycling of nylon-6 to short-chain oligomers and monomer ε-caprolactam via catalytic glycolysis is a potential solution for plastic waste remediation. Here, in this work, the kinetics of amide bond glycolysis (with ethylene glycol) in nylon-6 and the model compound N-phenethyl-3-phenylpropanamide (M1) were evaluated at 473 K in the presence of the cyclic amidine catalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene. Rates of polymer glycolysis were determined by the time-dependent shift in molecular weight distribution, whereas rates of M1 glycolysis were determined using liquid chromatography. The similarity of the first-order rate constants for glycolysis of nylon-6 and M1 at 473 K with 0.03 M amidine catalyst (5 mol% relative to amide bonds), 1.22 × 10 −5 s −1 and 2.18 × 10 −5 s −1 , respectively, confirmed the suitability of M1 as a model compound for nylon-6 glycolysis. Similar rates of glycolysis in the presence of other cyclic amidine catalysts as well as sodium methoxide revealed little influence of base strength. Glycolysis rates were unexpectedly non-linear in catalyst loading and deactivation occurred with long reaction times, presumably by non-selective decomposition of products as detected by liquid chromatography.

Depolymerization rate and rate constant↗
DOE OSTI2024

Pyrophosphate-free glycolysis in Clostridium thermocellum increases both thermodynamic driving force and ethanol titers

Background: Clostridium thermocellum is a promising candidate for production of cellulosic biofuels, however, its final product titer is too low for commercial application, and this may be due to thermodynamic limitations in glycolysis. Previous studies in this organism have revealed a metabolic bottleneck at the phosphofructokinase (PFK) reaction in glycolysis. In the wild-type organism, this reaction uses pyrophosphate (PP i ) as an energy cofactor, which is thermodynamically less favorable compared to reactions that use ATP as a cofactor. Previously we showed that replacing the PP i -linked PFK reaction with an ATP-linked reaction increased the thermodynamic driving force of glycolysis, but only had a local effect on intracellular metabolite concentrations, and did not affect final ethanol titer. Results: In this study, we substituted PP i -pfk with ATP-pfk, deleted the other PPi-requiring glycolytic gene pyruvate:phosphate dikinase (ppdk), and expressed a soluble pyrophosphatase (PPase) and pyruvate kinase (pyk) genes to engineer PP i -free glycolysis in C. thermocellum. We demonstrated a decrease in the reversibility of the PFK reaction, higher levels of lower glycolysis metabolites, and an increase in ethanol titer by an average of 38% (from 15.1 to 21.0 g/L) by using PP i -free glycolysis. Conclusions: By engineering PP i -free glycolysis in C. thermocellum, we achieved an increase in ethanol production. These results demonstrate that optimizing the thermodynamic landscape through metabolic engineering can enhance product titers. While further increases in ethanol titers are necessary for commercial application, this work represents a significant step toward engineering glycolysis in C. thermocellum to increase ethanol titers.

09 BIOMASS FUELS↗
DOE OSTI2018

Silencing PFKP inhibits starvation-induced autophagy, glycolysis, and epithelial mesenchymal transition in oral squamous cell carcinoma

Highlights: • The effect of starvation on glycolysis, autophagy and EMT in OSCC. • We verified the PFKP higher expression under starvation condition. • PFKP modulates starvation mediated glycolysis, autophagy, EMT of OSCC. • PFKP knockdown inhibits OSCC xenograft tumor growth. • The role of PFKP on clinicopathology in the progression of OSCC. The tumor starvation microenvironment plays a pivotal role in the malignant progression of cancer, which is closely related to autophagy, glycolysis, and epithelial mesenchymal transition (EMT). Nevertheless, the underlying mechanisms of the starvation-mediated malignant phenotype are still not well documented. In this study, we aimed to investigate the effect of starvation on glycolysis, autophagy, and EMT in OSCC and to further elucidate the key metabolic modulator. The results showed that starvation can induce autophagy, EMT, and enhanced glycolysis in OSCC cells. We determined that the expression of the key glycolytic enzyme phosphofructokinase-platelet (PFKP) obviously increased under starvation conditions and that PFKP knockdown inhibited starvation-mediated glycolysis, autophagy and EMT in OSCC cells. Moreover, we confirmed that PFKP knockdown inhibited OSCC xenograft growth in vivo. In addition, PFKP expression was significantly increased in OSCC patients and its upregulation was associated with the presence of tumor pathological differentiation and lymph node metastasis. Taken together, our findings demonstrate that PFKP is necessary for starvation-mediated autophagy, glycolysis, and EMT, thereby promoting the malignant progression of OSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Mitochondrial ATP generation is more proteome efficient than glycolysis

Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. Here, we accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Data for Mitochondrial ATP Generation is More Proteome Efficient than Glycolysis

Metabolic efficiency profoundly influences organismal fitness. Heterotrophs, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. While respiration is more energy-efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (i.e. faster). Through quantitative flux analysis and proteomics, we find however that mitochondrial respiration is actually more proteome-efficient than aerobic glycolysis. This is shown across yeasts, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which is valuable for hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth, but outgrow respiratory cells in oxygen limitation. Thus, aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

Metabolomics↗
DOE OSTI2016

miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells

miR-4458, a new tumor-suppressor, was reported to down-regulated in human hepatocellular carcinoma. The expression status, roles and inhibitory mechanisms of miR-4458 in other tumors still need to be clarified. The aim of this study is to investigate the effects of miR-4458 and to elucidate the potential mechanism in colon cancer cells. Using bioinformatic databases, we predicted that hexokinase2 (HK2), a rate-limiting enzyme in the glycolytic pathway, was a target of miR-4458, so the effects of miR-4458 on glycolysis and lactate production was assessed in colon cancer cells. We found that miR-4458 was down-regulated and HK2 was up-regulated in colon cancer cells. Overexpression of miR-4458 inhibited proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. Luciferase activity assays showed that HK2 was a direct target of miR-4458. Moreover, knockdown of HK2 by specific RNAi also suppressed proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. In conclusion, our findings suggested that miR-4458 inhibited the progression of colon cancer cells by inhibition of glycolysis and lactate production via directly targeting HK2 mRNA. - Highlights: • miR-4458 is down-regulated in colon cancer cells. • miR-4458 suppresses proliferation, glycolysis, and lactate production. • HK2 is a target of miR-4458. • HK2 knockdown inhibits proliferation, glycolysis, and lactate production.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Pristane promotes anaerobic glycolysis to facilitate proinflammatory activation of macrophages and development of arthritis

Highlights: • Pristane-induced arthritis is dependent on macrophages with M1 phenotype. • Pristane causes mitochondrial dysfunction and metabolic abnormalities in macrophages. • Macrophages treated by pristane show increased glycolysis flux and enzyme activity. • Metabolic reprogramming of macrophages controls M1 polarization and arthritis. Pristane-induced arthritis (PIA) could be adoptively transferred by splenic T cells in rats, and innate immunity should play critical roles in T cell activation. However, in pre-clinical stage, the activation mechanism of innate cells like macrophages remains unclear. Here we found that PIA was dependent on macrophages since cell depletion alleviated disease severity. Splenic macrophages of PIA rats showed M1 phenotypic shifting. The quantitative proteomics analysis suggested that macrophages initiated metabolic reprogramming with the conversion of aerobic oxidation to glycolysis in response to pristane in vivo. Notably, macrophages treated with pristane showed mitochondrial dysregulation and increased glycolysis flux and enzyme activity. Additionally, TNFα production, strongly associating with the glycolysis enzyme Ldha/Ldhb, could be reduced as glycolysis was inhibited or be enhanced as citrate cycle was blocked. This work provides detailed insights into the molecular mechanisms of pristane-mediated metabolic reprogramming in macrophages and suggests a new therapeutic strategy for arthritic disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Ad-apoptin inhibits glycolysis, migration and invasion in lung cancer cells targeting AMPK/mTOR signaling pathway

Ad-apoptin is a recombinant oncolytic adenovirus constructed by our laboratory that can express apoptin. It can selectively kill tumor cells without damaging normal cells. This study investigated the effects of Ad-apoptin on glycolysis, migration and invasion of non-small cell lung cancer. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, respectively. Glycolysis was investigated by glucose consumption, lactic acid production and glycolytic key enzyme protein levels. Migration and invasion were evaluated via wound healing, transwell assays and epithelial-mesenchymal transition (EMT) protein levels. The interaction between apoptin and AMPK was detected by Co-IP. A nude mice tumor model was established to investigate the anti-cancer role of Ad-apoptin in vivo. The results showed that Ad-apoptin inhibits cell viability and induces apoptosis of A549 and NCI–H23 cells. Ad-apoptin can reduce the glucose uptake and lactic production in lung cancer cells, and reduce the expression of related glycolysis-limiting enzymes. At the same time, Ad-apoptin inhibited the migration and invasion of lung cancer. Immunoprecipitation showed that apoptin and AMPK could interact directly. Moreover, knockdown of AMPK significantly attenuated the inhibitory effect of Ad-apoptin on glycolysis, migration and invasion of A549 and NCI–H23 cells. Ad-apoptin can inhibit the growth of tumors in nude mice. Compared with the control group, Ad-apoptin had a significant inhibitory effect on AMPK knockdown tumors. The immunohistochemical results of tumor tissues were consistent with those in vitro. Collectively, Ad-apoptin targets AMPK and inhibits glycolysis, migration and invasion of lung cancer cells through the AMPK/mTOR signaling pathway. This suggests that Ad-apoptin may have therapeutic potential for lung cancer by targeting AMPK activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells. - Highlights: • Blocking aerobic glycolysis is an approach to impair proliferation of cancer cells. • Small inhibitors of LDHA block aerobic glycolysis. • LDHA is also involved in the transcription of histone 2B gene. • LDHA inhibitors block histone 2B transcription. • LDHA inhibitors can hinder the proliferation also of non-glycolysing normal cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer

More and more evidence has demonstrated that Chromobox protein homolog 3(CBX3) has an important role in carcinogenesis by regulating several mechanisms, such as heterochromatin formation, gene silencing, DNA replication and repair. However, its role in pancreatic cancer has seldom been discussed. In the present study, we silenced CBX3 expression in pancreatic cancer cell lines and identified the positive roles of CBX3 in cancer cell proliferation. Furthermore, we demonstrated that silencing CBX3 in pancreatic cancer cells inhibited aerobic glycolysis, the basis for providing cancer cells with building blocks for macromolecule synthesis and ATP that required. To search for the underlying molecular mechanism, we turned to examine the impact of CBX3 on the expression of FBP1, a negative regulator of aerobic glycolysis in pancreatic cancer and indicated that CBX3 negatively regulated FBP1 expression. Silencing FBP1 expression attenuated the decrease in glycolytic capacity that caused by CBX3 knockdown in pancreatic cancer cells. Taken together, these data reveal that CBX3 serves as a positive regulator of aerobic glycolysis via suppressing of the FBP1 in pancreatic cancer cells. Disrupting the CBX3-FBP1 signaling axis would be effective to treat pancreatic cancer and prevent aerobic glycolysis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Near-equilibrium glycolysis supports metabolic homeostasis and energy yield

Glycolysis plays a central role in producing ATP and biomass. Its control principles, however, remain incompletely understood. In this work, we create a method that combines 2 H and 13 C tracers to determine glycolytic thermodynamics. With this method, we show that, in conditions and organisms with relatively slow fluxes, multiple steps in glycolysis are near to equilibrium, reflecting spare enzyme capacity. In Escherichia coli, nitrogen or phosphorus upshift rapidly increases the thermodynamic driving force, deploying the spare enzyme capacity to increase flux. Similarly, respiration inhibition in mammalian cells rapidly increases both glycolytic flux and the thermodynamic driving force. The thermodynamic shift allows flux to increase with only small metabolite concentration changes. Finally, we find that the cellulose-degrading anaerobe Clostridium cellulolyticum exhibits slow, near-equilibrium glycolysis due to the use of pyrophosphate rather than ATP for fructose-bisphosphate production, resulting in enhanced per-glucose ATP yield. Thus, near-equilibrium steps of glycolysis promote both rapid flux adaptation and energy efficiency.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Multiple GmWRI1s are redundantly involved in seed filling and nodulation by regulating plastidic glycolysis, lipid biosynthesis and hormone signalling in soybean ( Glycine max )

It has been reported that lipid biosynthesis in plant host root cells plays critical roles in legumefungal or -rhizobial symbioses, but little is known about its regulatory mechanism in legume– rhizobia interaction. Soybean WRINKLED1 (WRI1) a and b, with their alternative splicing (AS) products a’ and b’, are highly expressed in developing seeds and nodules, but their functions in soybean nodulation are not known. GmWRI1a and b differently promoted triacylglycerol (TAG) accumulation in both Arabidopsis wild-type and wri1 mutant seeds and when they ectopically expressed in the soybean hairy roots. Transcriptome analysis revealed that 15 genes containing AW boxes in their promoters were targeted by GmWRI1s, including genes involved in glycolysis, fatty acid (FA) and TAG biosynthesis. GmWRI1a, GmWRI1b and b’ differentially transactivated most targeted genes. Overexpression of GmWRI1s affected phospholipid and galactolipid synthesis, soluble sugar and starch contents and led to increased nodule numbers, whereas GmWRI1 knockdown hairy roots interfered root glycolysis and lipid biosynthesis and resulted in fewer nodules. These phenomena in GmWRI1 mutants coincided with the altered expression of nodulation genes. Thus, GmWRI1-regulated starch degradation, glycolysis and lipid biosynthesis were critical for nodulation. GmWRI1 mutants also altered auxin and other hormone-related biosynthesis and hormone-related genes, by which GmWRI1s may affect nodule development. The study expands the views for pleiotropic effects of WRI1s in regulating soybean seed filling and root nodulation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma

Hepatocellular Carcinoma (HCC) is a major form of liver cancer and a leading cause of cancer-related death worldwide. New insights into HCC pathobiology and mechanism of drug actions are urgently needed to improve patient outcomes. HCC undergoes metabolic reprogramming of glucose metabolism from respiration to aerobic glycolysis, a phenomenon known as the ‘Warburg Effect’ that supports rapid cancer cell growth, survival, and invasion. mTOR is known to promote Warburg Effect, but the underlying mechanism(s) remains poorly defined. The aim of this study is to understand the mechanism(s) and significance of mTOR regulation of aerobic glycolysis in HCC. We profiled mTORC1-dependent long non-coding RNAs (lncRNAs) by RNA-seq of HCC cells treated with rapamycin. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the transcriptional regulation of NEAT1 by mTORC1. [U- 13 C]-glucose labeling and metabolomic analysis, extracellular acidification Rate (ECAR) by Seahorse XF Analyzer, and glucose uptake assay were used to investigate the role of mTOR-NEAT1-NONO signaling in the regulation of aerobic glycolysis. RNA immunoprecipitation (RIP) and NONO-binding motif scanning were performed to identify the regulatory mechanism of pre-mRNA splicing by mTOR-NEAT1. Myristoylated AKT1 (mAKT1)/NRASV 12 -driven HCC model developed by hydrodynamic transfection (HDT) was employed to explore the significance of mTOR-NEAT1 signaling in HCC tumorigenesis and mTOR-targeted therapy. mTOR regulates lncRNA transcriptome in HCC and that NEAT1 is a major mTOR transcriptional target. Interestingly, although both NEAT1_1 and NEAT1_2 are down-regulated in HCC, only NEAT1_2 is significantly correlated with poor overall survival of HCC patients. NEAT1_2 is the organizer of nuclear paraspeckles that sequester the RNA-binding proteins NONO and SFPQ. We show that upon oncogenic activation, mTORC1 suppresses NEAT1_2 expression and paraspeckle biogenesis, liberating NONO/SFPQ, which in turn, binds to U5 within the spliceosome, stimulating mRNA splicing and expression of key glycolytic enzymes. This series of actions lead to enhanced glucose transport, aerobic glycolytic flux, lactate production, and HCC growth both in vitro and in vivo. Furthermore, the paraspeckle-mediated mechanism is important for the anticancer action of US FDA-approved drugs rapamycin/temsirolimus. These findings reveal a molecular mechanism by which mTOR promotes the ‘Warburg Effect’, which is important for the metabolism and development of HCC, and anticancer response of mTOR-targeted therapy.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1986

Models of glycolysis: Glyceraldehyde as a source of energy and monomers for prebiotic condensation reactions

All organisms require energy in a chemical form for maintenance and growth. In contemporary life this chemical energy is obtained by the synthesis of the phosphoanhydride bonds of ATP. Among the biological processes that yield ATP, fermentation is generally considered primitive, because it operates under anaerobic conditions by substrate-level phosphorylation which does not require compartmentation by membranes. Fermentation by the glycolytic pathway, which is found in almost every living cell, is an especially attractive energy source for primitive life. Glycolysis not only produces useful chemical energy (ATP), but intermediates of this pathway are also involved in amino acid synthesis and photosynthetic carbon-fixation. It is believed that energy and substrates needed for the origin of life were provided by nonenzymatic chemical reactions that resemble the enzyme-mediated reactions of glycolysis. These nonenzymatic reactions would have provided a starting point for the evolutionary development of glycolysis.

Weber, A. L.↗
DOE OSTI2018

Long non-coding RNA UCA1/miR-182/PFKFB2 axis modulates glioblastoma-associated stromal cells-mediated glycolysis and invasion of glioma cells

Glioblastoma (GB) is the most common and deadliest malignant primary brain tumor with a high recurrence. In this study, lncRNA UCA1/miR-182 axis has been regarded as a nodal driver of glioma invasion mediated by GB-associated stromal cells (GASCs) and GASC-secreted chemokine CXCL14. In clinical specimens, CXCL14 upregulation in GASCs also correlated with poor prognosis. Notably, CXCL14-high GASCs mediated lncRNA UCA1 upregulation and miR-182 downregulation in glioma cells. Moreover, miR-182 directly bound to the fructose-2,6-biphosphatase PFKFB2; UCA1/miR-182 axis thereby modulated GASC-induced glycolysis in glioma cells. Overall, UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion, glycolysis and invasion of glioma cells in GASCs.

60 APPLIED LIFE SCIENCES↗