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Diagnostics (Basel, Switzerland) Jan 2021Fibromyalgia (FM) is a highly prevalent syndrome that impairs the quality of life of the patients; however, its diagnosis is complex and mainly centered on pain... (Review)
Review
Fibromyalgia (FM) is a highly prevalent syndrome that impairs the quality of life of the patients; however, its diagnosis is complex and mainly centered on pain symptoms. The study of salivary biomarkers has proven highly useful for the diagnosis and prognosis of numerous diseases. The objective of this review was to gather published data on the utilization of salivary biomarkers to facilitate and complement the diagnosis of FM. Salivary biomarkers used in FM diagnosis include cortisol; calgranulin; and the enzymes α-amylase, transaldolase, and phosphoglycerate mutase. Increased serum levels of C-reactive protein, cytokines interleukin 1-β, interleukin 6, interleukin 8, interleukin 10, interleukin 17, tumor necrosis factor α, and various chemokines may serve as salivary biomarkers, given observations of their increased serum levels in patients with FM. Further research is warranted to study in depth the role and performance of biomarkers currently used in FM diagnosis/prognosis and to identify novel salivary biomarkers for this disease.
PubMed: 33401557
DOI: 10.3390/diagnostics11010063 -
IScience Oct 2023Mitophagy is critical for maintaining proper cellular functions, and it contributes to the onset and progression of osteoarthritis (OA). A recent study showed that...
Mitophagy is critical for maintaining proper cellular functions, and it contributes to the onset and progression of osteoarthritis (OA). A recent study showed that focused low-intensity pulsed ultrasound (FLIPUS) could activate mitophagy, but the molecular mechanism remains unclear. This study aimed to elucidate the chondroprotective effects of FLIPUS in OA and the regulatory effects on FUN14-domain containing 1 (FUNDC1-mediated mitophagy. , FLIPUS improved inflammatory response, anabolism, and catabolism in interleukin (IL)-1β-induced OA chondrocytes. The chondroprotective effects of FLIPUS were attributed to promoting the expression of phosphoglycerate mutase 5 (PGAM5) and the dephosphorylation of FUNDC1 at serine 13 (Ser13), as well as promoting the mitophagy process. , FLIPUS reduced the cartilage degeneration and apoptosis and reversed the change of anabolic- and catabolic-related proteins in destabilized medial meniscus (DMM)-induced mouse model. Thus, the study indicates that FLIPUS exhibits a chondroprotective effect via activating impaired FUNDC1-mediated mitophagy.
PubMed: 37720103
DOI: 10.1016/j.isci.2023.107772 -
Oncology Letters Jun 2018The aim of the present study was to examine the expression of phosphoglycerate mutase 1 (PGAM1) in astrocytomas, and to investigate its role in the progression of...
The aim of the present study was to examine the expression of phosphoglycerate mutase 1 (PGAM1) in astrocytomas, and to investigate its role in the progression of astrocytomas. The expression of PGAM1 mRNA in rat C6 glioma cells and normal astrocytes was determined using the reverse transcription-semi-quantitative polymerase chain reaction, and immunohistochemistry was used to detect the expression of PGAM1 protein in human astrocytomas and adjacent brain tissue. These data suggested that the expression of PGAM1 in rat C6 glioma cells was significantly increased compared with that of normal astrocytes (P<0.05), and the expression of PGAM1 protein in human astrocytoma tissue was significantly increased compared with that of the brain tissue surrounding the tumor (P<0.05). In addition, PGAM1 protein was more frequently expressed in high-grade astrocytomas compared with low-grade astrocytomas. These data indicate that the expression of PGAM1 is increased in C6 cells and human astrocytomas, and PGAM1 is probably involved in the tumorigenesis and progression of glioma, which may be a potential target for glioma treatment.
PubMed: 29805628
DOI: 10.3892/ol.2018.8477 -
Molecular Oncology Aug 2022Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis....
Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial-mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1-mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.
Topics: AMP-Activated Protein Kinases; Argininosuccinate Synthase; Breast Neoplasms; CCAAT-Enhancer-Binding Protein-beta; Cell Line, Tumor; Cell Proliferation; Female; Humans; Phosphoglycerate Mutase
PubMed: 35674458
DOI: 10.1002/1878-0261.13259 -
Clinical and Translational Medicine Dec 2023Hepatocellular carcinoma (HCC) cells undergo reprogramming of glucose metabolism to support uncontrolled proliferation, of which the intrinsic mechanism still merits...
BACKGROUND
Hepatocellular carcinoma (HCC) cells undergo reprogramming of glucose metabolism to support uncontrolled proliferation, of which the intrinsic mechanism still merits further investigation. Although regulatory factor X6 (RFX6) is aberrantly expressed in different cancers, its precise role in cancer development remains ambiguous.
METHODS
Microarrays of HCC tissues were employed to investigate the expression of RFX6 in tumour and adjacent non-neoplastic tissues. Functional assays were employed to explore the role of RFX6 in HCC development. Chromatin immunoprecipitation, untargeted metabolome profiling and sequencing were performed to identify potential downstream genes and pathways regulated by RFX6. Metabolic assays were employed to investigate the effect of RFX6 on glycolysis in HCC cells. Bioinformatics databases were used to validate the above findings.
RESULTS
HCC tissues exhibited elevated expression of RFX6. High RFX6 expression represented as an independent hazard factor correlated to poor prognosis in patients with HCC. RFX6 deficiency inhibited HCC development in vitro and in vivo, while its overexpression exerted opposite functions. Mechanistically, RFX6 bound to the promoter area of phosphoglycerate mutase 1 (PGAM1) and upregulated its expression. The increased PGAM1 protein levels enhanced glycolysis and further promoted the development of HCC.
CONCLUSIONS
RFX6 acted as a novel driver for HCC development by promoting aerobic glycolysis, disclosing the potential of the RFX6-PGAM1 axis for therapeutic targeting.
Topics: Humans; Carcinoma, Hepatocellular; Cell Proliferation; Glycolysis; Liver Neoplasms; Phosphoglycerate Mutase
PubMed: 38093528
DOI: 10.1002/ctm2.1511 -
Plant Signaling & Behavior 2014This review focuses on the energy metabolism during pollen maturation and tube growth and updates current knowledge. Pollen tube growth is essential for male... (Review)
Review
This review focuses on the energy metabolism during pollen maturation and tube growth and updates current knowledge. Pollen tube growth is essential for male reproductive success and extremely fast. Therefore, pollen development and tube growth are high energy-demanding processes. During the last years, various publications (including research papers and reviews) emphasize the importance of mitochondrial respiration and fermentation during male gametogenesis and pollen tube elongation. These pathways obviously contribute to satisfy the high energy demand, and there are many studies which suggest that respiration and fermentation are the only pathways to generate the needed energy. Here, we review data which show for the first time that in addition plastidial glycolysis and the balancing of the ATP/NAD(P)H ratio (by malate valves and NAD(+) biosynthesis) contribute to satisfy the energy demand during pollen development. Although the importance of energy generation by plastids was discounted during the last years (possibly due to the controversial opinion about their existence in pollen grains and pollen tubes), the available data underline their prime role during pollen maturation and tube growth.
Topics: Energy Metabolism; Fermentation; Mitochondria; Oxidation-Reduction; Plastids; Pollen Tube
PubMed: 25482752
DOI: 10.4161/15592324.2014.977200 -
Cancer Cell Nov 2012It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1...
It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
Topics: Animals; Binding, Competitive; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Gene Knockdown Techniques; Gluconates; Glucosephosphate Dehydrogenase; Glyceric Acids; Glycolysis; Humans; Mice; Mice, Nude; Models, Molecular; Neoplasms; Phosphoglycerate Mutase
PubMed: 23153533
DOI: 10.1016/j.ccr.2012.09.020 -
BMC Cancer Sep 2023Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for...
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs).
METHODS
MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis.
RESULTS
Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 (PGAM1), phosphoglycerate mutase 4 (PGAM4), nucleolar protein 6 (NOL6), nucleosome assembly protein 1 like 5 (NAP1L5), and sestrin1 (SESN1). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database.
CONCLUSION
MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1, PGAM4, NOL6, NAP1L5, and SESN1, which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Gene Expression Profiling; Lung Neoplasms; Phosphoglycerate Mutase; RNA, Long Noncoding
PubMed: 37667226
DOI: 10.1186/s12885-023-11347-7 -
Frontiers in Immunology 2023Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate...
INTRODUCTION
Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome.
OBJECTIVES
This study investigated the association between PGAM5 and gut microbiota in mice with TBI.
METHODS
The controlled cortical impact injury was established in mice with genetically-ablated () or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male mice or (). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected.
RESULTS
Treated with antibiotics for suppressing gut microbiota in mice partially relieved the role of deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. knockout exhibited an increased abundance of in mice. FMT from male mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI.
CONCLUSION
Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with -Nlrp3 contributing to peripheral effects.
Topics: Male; Animals; Mice; Neuroprotection; Neuroinflammatory Diseases; Phosphoglycerate Mutase; Verrucomicrobia; Brain Injuries, Traumatic; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 37287985
DOI: 10.3389/fimmu.2023.1172710 -
Journal of Cancer 2017Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential. However, no good biomarker has been identified to refine which subtype is...
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential. However, no good biomarker has been identified to refine which subtype is of high metastatic potential to make decisions regarding the elective and therapeutic management of lymphatic metastases. In this study, we investigated the role of the metabolic enzyme phosphoglycerate mutase 1 (PGAM1) in OSCC. PGAM1 expression was examined in tissue samples of 122 OSCC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazards model. Moreover, PGAM1 was knocked down in the OSCC cell lines Cal27 and HN12, followed by determination of the change in cell migration and signaling pathways. PGAM1 expression is correlated with age, lymphatic metastasis and tumor recurrence and is closely associated with poor overall survival (OS) and disease-free survival (DFS). Intriguingly, PGAM1 is an independent risk factor for OS and DFS. After knocking down PGAM1 in Cal27 and HN12 cells, cell migration was remarkably decreased along with signaling pathway molecules, such as proto-oncogene c-SRC (SRC), Focal adhesion kinase (FAK) and Paxillin. The effect on cell migration was abolished following pretreatment with an SRC inhibitor. This study suggested that PGAM1 is a poor prognostic biomarker of OSCC and may be used to select patients of high metastatic potential in the clinic, and PGAM1 promotes the migration of OSCC cells is associated with the SRC pathway.
PubMed: 28819393
DOI: 10.7150/jca.19278