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Cancer Cell International Sep 2021Phosphoglucomutase 1 (PGM1) acts as an important regulator in glucose metabolism. However, the role of PGM1 in gastric cancer (GC) remains unclear. This study aims to...
BACKGROUND
Phosphoglucomutase 1 (PGM1) acts as an important regulator in glucose metabolism. However, the role of PGM1 in gastric cancer (GC) remains unclear. This study aims to investigate the role of PGM1 and develop novel regimens based on metabolic reprogramming in GC.
METHODS
Correlation and enrichment analyses of PGM1 were conducted based on The Cancer Genome Atlas database. Data derived from the Kaplan-Meier Plotter database were analyzed to evaluate correlations between PGM1 expression and survival time of GC patients. Cell counting kit-8, 5-Ethynyl-2-deoxyuridine, flow cytometry assays, generation of subcutaneous tumor and lung metastasis mouse models were used to determine growth and metastasis in vitro and in vivo. Cell glycolysis was detected by a battery of glycolytic indicators, including lactate, pyruvic acid, ATP production and glucose uptake. Fatty Acid Synthase (FASN) activity and expression levels of lipid enzymes were determined to reflect on lipid metabolism.
RESULTS
Correlation and enrichment analyses suggested that PGM1 was closely associated with cell viability, proliferation and metabolism. PGM1 was overexpressed in GC tissues and cell lines. High PGM1 expression served as an indicator of shorter survival for specific subpopulation of GC patients. It was also correlated with pathological tumor stage and pathological tumor node metastasis stage of GC. Under the glucose deprivation condition, knockdown of PGM1 significantly suppressed cell viability, proliferation and glycolysis, whereas lipid metabolism was enhanced. Orlistat, as a drug that was designed to inhibit FASN activity, effectively induced apoptosis and suppressed lipid metabolism in GC. However, orlistat conversely increased glycolytic levels. Orlistat exhibited more significant inhibitive effects on GC progression after knockdown of PGM1 under glucose deprivation due to combination of glycolysis and lipid metabolism both in vitro and in vivo.
CONCLUSIONS
Downregulation of PGM1 expression under glucose deprivation enhanced anti-cancer effects of orlistat. This combination application may serve as a novel strategy for GC treatment.
PubMed: 34507580
DOI: 10.1186/s12935-021-02193-3 -
Animal Bioscience Jan 2022Sarcoplasmic proteins include proteins that play critical roles in biological processes of living organisms. How seasons influence biological processes and meat quality...
OBJECTIVE
Sarcoplasmic proteins include proteins that play critical roles in biological processes of living organisms. How seasons influence biological processes and meat quality of postmortem muscles through the regulation of protein phosphorylation remain to be investigated. In this study, the phosphorylation of sarcoplasmic proteins in pork longissimus muscle was investigated in four seasons.
METHODS
Sarcoplasmic proteins were extracted from 40 pork carcasses (10 for each season) and analyzed through ProQ Diamond staining for phosphorylation labeling and Sypro Ruby staining for total protein labeling. The pH of muscle, contents of glycogen and ATP were measured at 45 min, 3 h, and 9 h postmortem and the water (P2b, P21, and P22) was measured at 3 h and 9 h.
RESULTS
A total of 21 bands were detected. Band 8 (heat shock cognate 71 kDa protein; heat shock 70 kDa protein 1B) had higher phosphorylation level in summer than that in other seasons at 45 min postmortem. The phosphorylation levels of 3 Bands were significantly different between fast and normal pH decline groups (p<0.05). The phosphorylation levels of 4 bands showed negative associations with immobilized water (P21) and positive association with free water (P22).
CONCLUSION
The phosphorylation levels of sarcoplasmic proteins involved in energy metabolism and heat stress response at early postmortem time differed depending on the seasons. These proteins include heat shock protein 70, pyruvate kinase, phosphoglucomutase-1, glucose-6-phosphate isomerase, and carbonic anhydrase 3. High temperatures in summer might result in the phosphorylation of those proteins, leading to pH decline and low water holding capacity.
PubMed: 34474534
DOI: 10.5713/ab.21.0185 -
International Journal of Medical... Aug 2021Many models assessing the risk of sepsis utilize the knowledge of the constituents of the plasminogen system, as it is proven that some species of bacteria can activate...
Many models assessing the risk of sepsis utilize the knowledge of the constituents of the plasminogen system, as it is proven that some species of bacteria can activate plasminogen, as a result of interactions with bacterial outer membrane proteins. However, much is yet to be discovered about this interaction since there is little information regarding some bacterial species. This study is aimed to check if Klebsiella pneumoniae, one of the major factors of nosocomial pneumonia and a factor for severe sepsis, has the ability to bind to human plasminogen. The strain used in this study, PCM 2713, acted as a typical representative of the species. With use of various methods, including: electron microscopy, 2-dimensional electrophoresis, immunoblotting and peptide fragmentation fingerprinting, it is shown that Klebsiella pneumoniae binds to human plasminogen, among others, due to plasminogen-bacterial enolase-like protein interaction, occurring on the outer membrane of the bacterium. Moreover, the study reveals, that other proteins, such as: phosphoglucomutase, and phosphoenolpyruvate carboxykinase act as putative plasminogen-binding factors. These information may virtually act as a foundation for future studies investigating: the: pathogenicity of Klebsiella pneumoniae and means for prevention from the outcomes of Klebsiella-derived sepsis.
Topics: Bacterial Outer Membrane Proteins; Humans; Immunoblotting; Klebsiella pneumoniae; Phosphopyruvate Hydratase; Plasminogen
PubMed: 34237624
DOI: 10.1016/j.ijmm.2021.151518 -
Bioscience Reports Jul 2021Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in...
BACKGROUND
Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in CRC patients as diagnostic markers for early-stage CRC.
METHODS
Using Gene Expression Omnibus (GEO) datasets GSE102340, GSE126092, GSE109454 and GSE115856, 14 differentially expressed lncRNAs were identified between cancer and adjacent tissues, among which, the two most differentially expressed were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR) in 200 healthy controls and 188 CRC patients. A receiver operating characteristic (ROC) analysis was employed to evaluate the diagnostic accuracy for CRC.
RESULTS
From four GEO datasets, three up-regulated and eleven down-regulated lncRNAs were identified in CRC tissues, among which, lncRNA urothelial carcinoma-associated 1 (UCA1) and lncRNA phosphoglucomutase 5-antisense RNA 1 (PGM5-AS1) were the most significantly up- and down-regulated lncRNAs in CRC patient plasma, respectively. The area under the ROC curve was calculated to be 0.766, 0.754 and 0.798 for UCA1, PGM5-AS1 and the combination of these two lncRNAs, respectively. Moreover, the diagnostic potential of these two lncRNAs was even higher for the early stages of CRC. The combination of UCA1 and PGM5-AS1 enhanced the AUC to 0.832, and when the lncRNAs were used with carcinoembryonic antigen (CEA), the AUC was further improved to 0.874.
CONCLUSION
In the present study, we identified two lncRNAs, UCA1 and PGM5-AS1, in CRC patients' plasma, which have the potential to be used as diagnostic biomarkers of CRC.
Topics: Biomarkers, Tumor; Case-Control Studies; Cell-Free Nucleic Acids; Colorectal Neoplasms; Databases, Genetic; Female; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; RNA, Long Noncoding; Reproducibility of Results
PubMed: 34212174
DOI: 10.1042/BSR20211115 -
Journal of Bacteriology Jun 2021
Topics: Bacterial Capsules; Biosynthetic Pathways; Phosphoglucomutase; Streptococcus pneumoniae
PubMed: 34100630
DOI: 10.1128/JB.00220-21 -
International Journal of Molecular... May 2021Rice ( L.) is a foremost staple food for approximately half the world's population. The components of rice starch, amylose, and amylopectin are synthesized by a series... (Review)
Review
Rice ( L.) is a foremost staple food for approximately half the world's population. The components of rice starch, amylose, and amylopectin are synthesized by a series of enzymes, which are responsible for rice starch properties and functionality, and then affect rice cooking and eating quality. Recently, proteomics technology has been applied to the establishment of the differentially expressed starch biosynthesis-related proteins and the identification of posttranslational modifications (PTMs) target starch biosynthesis proteins as well. It is necessary to summarize the recent studies in proteomics and PTMs in rice endosperm to deepen our understanding of starch biosynthesis protein expression and regulation, which will provide useful information to rice breeding programs and industrial starch applications. The review provides a comprehensive summary of proteins and PTMs involved in starch biosynthesis based on proteomic studies of rice developing seeds. Starch biosynthesis proteins in rice seeds were differentially expressed in the developing seeds at different developmental stages. All the proteins involving in starch biosynthesis were identified using proteomics methods. Most starch biosynthesis-related proteins are basically increased at 6-20 days after flowering (DAF) and decreased upon the high-temperature conditions. A total of 10, 14, 2, 17, and 7 starch biosynthesis related proteins were identified to be targeted by phosphorylation, lysine acetylation, succinylation, lysine 2-hydroxyisobutyrylation, and malonylation, respectively. The phosphoglucomutase is commonly targeted by five PTMs types. Research on the function of phosphorylation in multiple enzyme complex formation in endosperm starch biosynthesis is underway, while the functions of other PTMs in starch biosynthesis are necessary to be conducted in the near future.
Topics: Biosynthetic Pathways; Gene Expression Regulation, Plant; Oryza; Phosphorylation; Plant Development; Plant Proteins; Protein Processing, Post-Translational; Proteome; Proteomics; Seeds; Starch
PubMed: 34072759
DOI: 10.3390/ijms22115901 -
Microorganisms May 2021subsp. () is a plant pathogenic bacterium causing citrus canker disease. The gene encodes a phosphoglucomutase/phosphomannomutase protein that is a key enzyme...
subsp. () is a plant pathogenic bacterium causing citrus canker disease. The gene encodes a phosphoglucomutase/phosphomannomutase protein that is a key enzyme required for the synthesis of lipopolysaccharides and exopolysaccharides in Xanthomonads. In this work, firstly we isolated a transposon mutant (::Tn5) and analyzed its phenotypes as biofilm formation, xanthan gum production, and pathogenesis on the sweet orange host. Moreover, to confirm the role in the impaired phenotypes we further produced a non-polar deletion mutant (Δ) and performed the complementation of both mutants. In addition, we analyzed the percentages of the xanthan gum monosaccharides produced by wild-type and mutant. The mutant strain had higher ratios of mannose, galactose, and xylose and lower ratios of rhamnose, glucuronic acid, and glucose than the wild-type strain. Such changes in the saccharide composition led to the reduction of xanthan yield in the deficient strain, affecting also other important features in , such as biofilm formation and sliding motility. Moreover, we showed that ::Tn5 caused no symptoms on host leaves after spraying, a method that mimetics the natural infection condition. These results suggest that plays an important role in the epiphytical stage on the leaves that is essential for the successful interaction with the host, including adaptive advantage for bacterial survival and host invasion, which culminates in pathogenicity.
PubMed: 34072545
DOI: 10.3390/microorganisms9061176 -
The New Phytologist Aug 2021Rice (Oryza sativa) tiller angle is a key component for achieving ideal plant architecture and higher grain yield. However, the molecular mechanism underlying rice...
Rice (Oryza sativa) tiller angle is a key component for achieving ideal plant architecture and higher grain yield. However, the molecular mechanism underlying rice tiller angle remains elusive. We characterized a novel rice tiller angle mutant lazy2 (la2) and isolated the causative gene LA2 through map-based cloning. Biochemical, molecular and genetic studies were conducted to elucidate the LA2-involved tiller angle regulatory mechanism. The la2 mutant shows large tiller angle with impaired shoot gravitropism and defective asymmetric distribution of auxin. We found that starch granules in amyloplasts are completely lost in the gravity-sensing leaf sheath base cells of la2, whereas the seed development is not affected. LA2 encodes a novel chloroplastic protein that can interact with the starch biosynthetic enzyme Oryza sativa plastidic phosphoglucomutase (OspPGM) to regulate starch biosynthesis in rice shoot gravity-sensing cells. Genetic analysis showed that LA2 regulates shoot gravitropism and tiller angle by acting upstream of LA1 to mediate lateral auxin transport. Our studies revealed that LA2 acts as a novel regulator of rice tiller angle by specifically regulating starch biosynthesis in gravity-sensing cells, and established the framework of the starch-statolith-dependent rice tiller angle regulatory pathway, providing new insights into the rice tiller angle regulatory network.
Topics: Gene Expression Regulation, Plant; Gravitropism; Oryza; Plant Proteins; Starch
PubMed: 34042184
DOI: 10.1111/nph.17426 -
Journal of Oncology 2021Metabolic reprogramming of aerobic glycolysis is a hallmark of cancer cells. Regulators of aerobic glycolysis have become targets for cancer diagnosis and therapy....
Metabolic reprogramming of aerobic glycolysis is a hallmark of cancer cells. Regulators of aerobic glycolysis have become targets for cancer diagnosis and therapy. However, the regulators of aerobic glycolysis in breast cancer development have not been well elucidated. Here, we show that the phosphoglucomutase (PGM) family member PGM5 promotes conversion of glucose-1-phosphate (G1P) into glucose-6-phosphate (G6P) and inhibits breast cancer cell proliferation and migration through regulating aerobic glycolysis. In breast cancer patients, PGM5 is significantly downregulated, and its low expression is a predictor of poor prognosis. MicroRNA-1224-3p (miR-1224-3p) inhibits the PGM5 level through directly targeting its 3'-untranslated region and suppresses PGM5-mediated breast cancer cell proliferation, migration, and glycolytic function. Moreover, the miR-1224-3p/PGM5 axis regulates the expression of cell cycle- and apoptosis-related genes and the markers of epithelial-mesenchymal transition (EMT), a process involved in migration and metastasis of cancer cells. Taken together, our results indicate that miR-1224-3p/PGM5 axis plays important roles in breast cancer cell proliferation, migration, and aerobic glycolysis and may be a potential target for breast cancer therapy.
PubMed: 33986801
DOI: 10.1155/2021/5529770 -
American Journal of Human Genetics Jun 2021We describe a genetic syndrome due to PGM2L1 deficiency. PGM2 and PGM2L1 make hexose-bisphosphates, like glucose-1,6-bisphosphate, which are indispensable cofactors for...
We describe a genetic syndrome due to PGM2L1 deficiency. PGM2 and PGM2L1 make hexose-bisphosphates, like glucose-1,6-bisphosphate, which are indispensable cofactors for sugar phosphomutases. These enzymes form the hexose-1-phosphates crucial for NDP-sugars synthesis and ensuing glycosylation reactions. While PGM2 has a wide tissue distribution, PGM2L1 is highly expressed in the brain, accounting for the elevated concentrations of glucose-1,6-bisphosphate found there. Four individuals (three females and one male aged between 2 and 7.5 years) with bi-allelic inactivating mutations of PGM2L1 were identified by exome sequencing. All four had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Analysis of the children's fibroblasts showed that glucose-1,6-bisphosphate and other sugar bisphosphates were markedly reduced but still present at concentrations able to stimulate phosphomutases maximally. Hence, the concentrations of NDP-sugars and glycosylation of the heavily glycosylated protein LAMP2 were normal. Consistent with this, serum transferrin was normally glycosylated in affected individuals. PGM2L1 deficiency does not appear to be a glycosylation defect, but the clinical features observed in this neurodevelopmental disorder point toward an important but still unknown role of glucose-1,6-bisphosphate or other sugar bisphosphates in brain metabolism.
Topics: Alleles; Child; Child, Preschool; Female; Glucose-6-Phosphate; Glycosylation; Humans; Male; Mutation; Neurodevelopmental Disorders; Pedigree; Phosphotransferases
PubMed: 33979636
DOI: 10.1016/j.ajhg.2021.04.017