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Cancer Biotherapy & Radiopharmaceuticals Dec 2022Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate...
Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.
PubMed: 36576783
DOI: 10.1089/cbr.2022.0039 -
Cell Biology International Apr 2023Gliomas account for about 80% of malignant brain tumors. The incidence of a new brain tumor is 6.4 per 100,000 persons per year with an overall 5-year survival rate of...
Gliomas account for about 80% of malignant brain tumors. The incidence of a new brain tumor is 6.4 per 100,000 persons per year with an overall 5-year survival rate of 33.4%. Regardless of the great advances that have been made in recent years, the causes and pathogenesis of glioma remain unclear. Here we study how phosphoglycerate mutase 4 (PGAM4) contributes to glioma. Using a variety of methods to examine glioma cell viability, proliferation, apoptosis, glycolysis, as well as ChIP coanalysis with modified histone H3, we showed that PGAM4 was significantly upregulated in patients with glioma and associated with poor survival. Silencing PGAM4 attenuated cell viability, proliferation, and glycolysis in T98G cells and suppressed tumor growth in vivo, while overexpressing PGAM4 promoted cell viability, proliferation, and glycolysis in U251 cells via regulating glycolysis pathway. Study also revealed that PGAM4 was regulated by EP300-mediated modifications of H3K27ac. PGAM4 silencing inhibited cell viability and proliferation, suppressed tumor growth, and decreased chemoresistance to temozolomide in glioma cells through suppressing glycolysis.
Topics: Humans; Temozolomide; Phosphoglycerate Mutase; Drug Resistance, Neoplasm; Glioma; Brain Neoplasms; Apoptosis; Glycolysis; Cell Line, Tumor; Cell Proliferation
PubMed: 36576012
DOI: 10.1002/cbin.11983 -
Frontiers in Plant Science 2022() is a gram-negative bacterium that causes bacterial fruit blotch (BFB) disease in cucurbit crops including watermelon. However, despite the great economic losses...
A putative 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase is involved in the virulence, carbohydrate metabolism, biofilm formation, twitching halo, and osmotic tolerance in .
() is a gram-negative bacterium that causes bacterial fruit blotch (BFB) disease in cucurbit crops including watermelon. However, despite the great economic losses caused by this disease worldwide, -resistant watermelon cultivars have not been developed. Therefore, characterizing the virulence factors/mechanisms of would enable the development of effective control strategies against BFB disease. The 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (BdpM) is known to participate in the glycolysis and gluconeogenesis pathways. However, the roles of the protein have not been characterized in . To elucidate the functions of BdpmAc (Bdpm in ), comparative proteomic analysis and diverse phenotypic assays were conducted using a knockout mutant () and a wild-type strain. The virulence of the mutant to watermelon was remarkably reduced in both germinated seed inoculation and leaf infiltration assays. Moreover, the mutant could not grow with fructose or pyruvate as a sole carbon source. However, the growth of the mutant was restored to levels similar to those of the wild-type strain in the presence of both fructose and pyruvate. Comparative proteomic analyses revealed that diverse proteins involved in motility and wall/membrane/envelop biogenesis were differentially abundant. Furthermore, the mutant exhibited decreased biofilm formation and twitching halo size. Interestingly, the mutant exhibited a higher tolerance against osmotic stress. Overall, our findings suggest that BdpmAc affects the virulence, glycolysis/gluconeogenesis, biofilm formation, twitching halo size, and osmotic tolerance of , suggesting that this protein has pleiotropic properties. Collectively, our findings provide fundamental insights into the functions of a previously uncharacterized phosphoglycerate mutase in .
PubMed: 36438092
DOI: 10.3389/fpls.2022.1039420 -
Frontiers in Aging Neuroscience 2022We aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson's disease (PD) diagnosis as well as its association with...
BACKGROUND
We aimed to examine whether plasma-derived phosphoglycerate mutase 5 (PGAM5) can be a biomarker for Parkinson's disease (PD) diagnosis as well as its association with the severity of motor/non-motor manifestations of PD.
METHODS
We enrolled 124 patients with PD (PD group) and 50 healthy controls (HC group). We measured plasma PGAM5 levels using a quantitative sandwich enzyme immunoassay. Patients with PD underwent baseline evaluations using the Unified Parkinson's Disease Rating Scale (UPDRS), while participants in both groups were evaluated using scales for non-motor manifestations. Receiver operating characteristic curves were used to evaluate the predictive utility of plasma PAMG5 alone and combined with other factors.
RESULTS
Plasma PAMG5 levels were significantly higher in the PD group; the area under the curve (AUC) of plasma PGAM5 levels alone was 0.76. The AUC values for elderly participants and patients without hypertension were 0.78 and that for was 0.79. Notably, plasma PGAM5 levels combined with plasma oligomeric α-synuclein (α-syn) and the score of the REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) showed AUC values of 0.80 and 0.82. Multivariable logistic analysis revealed that plasma PAMG5 levels were independently associated with PD (odds ratio,1.875 [95% confidence interval 1.206-2.916], = 0.005) but not the severity of motor/non-motor manifestations of PD.
CONCLUSION
Plasma PGAM5 is an independent biomarker for PD, especially among elderly patients (age > 60 years) and patients without hypertension. The predictive utility of PGAM5 was improved when combined with plasma oligomeric α-syn or the RBDQ-HK score.
PubMed: 36389083
DOI: 10.3389/fnagi.2022.1022274 -
International Journal of Molecular... Oct 2022Phosphoglycerate mutase (PGAM) is a glycolytic enzyme converting 3-phosphoglycerate to 2-phosphoglycerate, which in mammalian cells is expressed in two isoforms: brain...
Phosphoglycerate mutase (PGAM) is a glycolytic enzyme converting 3-phosphoglycerate to 2-phosphoglycerate, which in mammalian cells is expressed in two isoforms: brain (PGAM1) and muscle (PGAM2). Recently, it was shown that besides its enzymatic function, PGAM2 can be imported to the cell nucleus where it co-localizes with the nucleoli. It was suggested that it functions there to stabilize the nucleolar structure, maintain mRNA expression, and assist in the assembly of new pre-ribosomal subunits. However, the precise mechanism by which the protein translocates to the nucleus is unknown. In this study, we present the first crystal structure of PGAM2, identify the residues involved in the nuclear localization of the protein and propose that PGAM contains a "quaternary nuclear localization sequence (NLS)", i.e., one that consists of residues from different protein chains. Additionally, we identify potential interaction partners for PGAM2 in the nucleoli and demonstrate that 14-3-3ζ/δ is indeed an interaction partner of PGAM2 in the nucleus. We also present evidence that the insulin/IGF1-PI3K-Akt-mTOR signaling pathway is responsible for the nuclear localization of PGAM2.
Topics: Animals; Phosphoglycerate Mutase; Active Transport, Cell Nucleus; Phosphatidylinositol 3-Kinases; 14-3-3 Proteins; Muscles; Mammals
PubMed: 36361985
DOI: 10.3390/ijms232113198 -
Cell Biology International Jan 2023Triple-negative breast cancer (TNBC) is a malignancy with high metastasis rate and poor prognosis. Limited drugs are effective for the treatment of TNBC patients....
Triple-negative breast cancer (TNBC) is a malignancy with high metastasis rate and poor prognosis. Limited drugs are effective for the treatment of TNBC patients. Ubiquitin specific proteases (USPs) are important posttranscription modulators that promote protein stability by reducing the ubiquitination of the proteins. Aberrant expression of USPs is involved in the development of numerous cancers. However, it remains poorly understood on the role of USP46 in TNBC growth and metastasis. In this study, we explored the clinical relevance, function and molecular mechanisms of USP46 in TNBC. USP46 expression was increased in breast cancer tissues. High expression of USP46 was associated with the poorer prognosis of the patients. Overexpression and knockdown experiments demonstrated that USP46 was critical for TNBC cell growth, migration, and tumorigenesis. Mechanistically, USP46 enhanced the protein stability of phosphoglycerate mutase 1 (PGAM1) via direct interaction. Importantly, USP46 stimulated the glycolysis and promoted the malignant growth of TNBC cells through upregulation of PGAM1. Our study reveals that USP46/PGAM1 axis contributes to TNBC progression and is a potential target for the treatment of TNBC patients.
Topics: Humans; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glycolysis; Phosphoglycerate Mutase; Triple Negative Breast Neoplasms; Ubiquitin-Specific Proteases
PubMed: 36335636
DOI: 10.1002/cbin.11937 -
Toxicology Letters Jan 2023The pathophysiology of renal lipid toxicity caused by excess adiposity is not well-understood. Necroptosis, a regulated form of cell death, is involved in injuring renal...
The pathophysiology of renal lipid toxicity caused by excess adiposity is not well-understood. Necroptosis, a regulated form of cell death, is involved in injuring renal tubular epithelial cells (RTECs). Phosphoglycerate mutase 5 (PGAM5) is a key downstream effector of necroptosis. This study investigated the underlying mechanism of PGAM5 in promoting lipid-induced necroptosis in RTECs. HK2 cells (an immortalized proximal tubule epithelial cell line) were exposed to oleic acid (OA) to mimic the lipid overload environment in vitro. We found that OA suppressed HK2 cell proliferation, triggered cytoskeleton rupture and cell death. In OA-treated cells, upregulated expression of necroptosis pathway proteins, phosphorylated receptor-interacting protein-1/3 (pRIPK1/3), phosphorylated mixed lineage kinase domain-like protein (pMLKL), PGAM5, phosphorylated dynamin-related protein 1 (pDRP1), and downregulated pDRP1 expression were observed. This was accompanied by mitochondrial dysfunction (mitochondrial ROS overproduction and decreased mitochondrial membrane potential) and increased cellular necrosis, as reflected by Annexin V/ Propidium Iodide (PI) labeling. OA also induced the accumulation of LC3II and P62, blocking autophagosome fusion with lysosomes. Knockdown of PGAM5 could prevent these OA-induced changes. We propose inhibition of PGAM5 protects lipid-induced RTECs from necroptosis by reducing DRP1-mediated mitochondrial fission and improving mitophagy flux.
Topics: Mitophagy; Mitochondrial Dynamics; Necroptosis; Phosphoglycerate Mutase; Epithelial Cells; Lipids; Mitochondrial Proteins
PubMed: 36273635
DOI: 10.1016/j.toxlet.2022.10.003 -
Growth Factors (Chur, Switzerland) Nov 2022This study explored the impacts of matrine on hepatocellular carcinoma (HCC) cell growth, metastasis, epithelial-mesenchymal transition (EMT), and stemness through...
This study explored the impacts of matrine on hepatocellular carcinoma (HCC) cell growth, metastasis, epithelial-mesenchymal transition (EMT), and stemness through regulating the microRNA / () axis. The association between expression with the prognosis of HCC patients was studied. and sequences were transfected into matrine-treated HCC cells, and cell proliferation, invasion, apoptosis, and stemness were detected, as well as protein expression of EMT- and stemness-related makers. The targeting relationship between and was identified. Matrine elevated expression, repressed proliferation, invasion, and anti-apoptosis of HCC cells, and constrained EMT and stemness . was a target of . Repression of rescued the effects of downregulation on HCC cells. Matrine stimulates HCC cell apoptosis and represses the process of EMT and stemness through the / axis.
Topics: Humans; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Liver Neoplasms; MicroRNAs; Phosphoglycerate Mutase; Apoptosis; Matrines
PubMed: 36260520
DOI: 10.1080/08977194.2022.2113073 -
International Journal of Molecular... Sep 2022Stressors cause activation of the hypothalamic-pituitary-adrenal (HPA) axis and a systemic inflammatory response. As a newly proposed cell death manner in recent years,...
Stressors cause activation of the hypothalamic-pituitary-adrenal (HPA) axis and a systemic inflammatory response. As a newly proposed cell death manner in recent years, necroptosis occurs in a variety of tissue damage and inflammation. However, the role of necroptosis in HPA axis activation remains to be elucidated. The aim of this study was to investigate the occurrence of necroptosis and its role in HPA activation in a porcine stress model induced by lipopolysaccharide (LPS). Several typical stress behaviors like fever, anorexia, shivering and vomiting were observed in piglets after LPS injection. HPA axis was activated as shown by increased plasma cortisol concentration and mRNA expression of pituitary corticotropin-releasing hormone receptor 1 () and adrenal steroidogenic acute regulatory protein (). The mRNA expression of tumor necrosis factor α (), interleukin-1β () and in the hypothalamus, pituitary gland and adrenal gland was elevated by LPS, accompanied by the activation of necroptosis indicated by higher mRNA expression of necroptosis signals including receptor-interacting protein kinase (RIP) 1, RIP3, and phosphorylated mixed-lineage kinase domain-like protein (MLKL). Furthermore, necrostatin-1 (Nec-1), an inhibitor of necroptosis, inhibited necroptosis indicated by decreased mRNA levels of , , , and phosphoglycerate mutase family member 5 () in the hypothalamus, pituitary gland and adrenal gland. Nec-1 also decreased the mRNA expression of and and inhibited the activation of the HPA axis indicated by lower plasma cortisol concentration and mRNA expression of adrenal type 2 melanocortin receptor () and . These findings suggest that necroptosis is present and contributes to HPA axis activation induced by LPS. These findings provide a potential possibility for necroptosis as an intervention target for alleviating HPA axis activation and stress responses.
Topics: Animals; Corticotropin-Releasing Hormone; Hydrocortisone; Hypothalamo-Hypophyseal System; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Necroptosis; Phosphoglycerate Mutase; Pituitary-Adrenal System; Protein Kinases; RNA, Messenger; Swine; Tumor Necrosis Factor-alpha
PubMed: 36232518
DOI: 10.3390/ijms231911218 -
Frontiers in Bioscience (Landmark... Sep 2022Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague.
BACKGROUND
Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague.
METHODS
Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3. Cell Counting Kit-8 proliferation experiment, plasmids and siRNA transfection, pyruvic acid and lactic acid production detection, immunofluorescence staining of functional mitochondria and oxygen consumption rate and extracellular acidification rate measurement were uesd to assess the glycolytic metabolism and paclitaxel resistance in ovarian cancer cells. The expression and prognostic effect of PGAM1 in 180 ovarian cancer patients were analyzed.
RESULTS
SKOV3-TR30 cells display higher glycolytic flux and lower mitochondrial function than SKOV3 cells. Down-regulation of PGAM1 in SKOV3-TR30 cells resulted in decreased paclitaxel resistance. Up-regulation of PGAM1 in SKOV3 cells led to enhanced paclitaxel resistance. Analysis of the glycolytic flux revealed that PGAM1-mediated pyruvic acid or lactic acid production could modulate the capabilities of ovarian cancer cell resistance to paclitaxel. Our data also show high expression of PGAM1 as significantly correlated with reduced overall survival and reduced progression free survival in ovarian cancer patients.
CONCLUSIONS
PGAM1 acts to promote paclitaxel resistance via pyruvic acid and/or lactate production in ovarian cancer cells. Inhibiting PGAM1 may provide a new approach to favorably alter paclitaxel resistance in ovarian cancer.
Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Female; Glycolysis; Humans; Lactic Acid; Ovarian Neoplasms; Paclitaxel; Phosphoglycerate Mutase; Pyruvic Acid; RNA, Small Interfering
PubMed: 36224008
DOI: 10.31083/j.fbl2709262