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BMC Cancer Apr 2024Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and...
BACKGROUND
Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear.
METHODS
In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC.
RESULTS
The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis.
CONCLUSION
Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis.
Topics: Animals; Female; Humans; Male; Mice; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Down-Regulation; Gene Expression Regulation, Neoplastic; Membrane Proteins; Mice, Nude; MicroRNAs; Neoplasm Invasiveness; Phosphoglycerate Dehydrogenase; RNA, Circular; Thyroid Cancer, Papillary; Thyroid Neoplasms; Pyruvate Kinase
PubMed: 38654205
DOI: 10.1186/s12885-024-12199-5 -
Frontiers in Microbiology 2024DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of variety "Qing Yan 1".
INTRODUCTION
DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of variety "Qing Yan 1".
METHODS
To elucidate the transcriptomic changes in the oat root system following interaction with DGL1 and to reveal the molecular mechanism by which DGL1 promotes oat growth, treatment and control groups of oat roots at 2, 4, 8, and 12 h after inoculation with a suspension of strain DGL1 were analyzed using Illumina high-throughput transcriptome sequencing technology. The differentially expressed genes were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the metabolic pathways and key genes were analyzed.
RESULTS
The results showed that 7874, 13,392, 13,169, and 19,026 differentially expressed genes were significantly enriched in the glycolysis/gluconeogenesis pathway, amino acid metabolism, nitrogen metabolism, plant hormone signal transduction, and other related metabolic pathways in the oat roots at 2, 4, 8, and 12 h after inoculation with a DGL1 suspension. The GO and KEGG enrichment analyses revealed that the genes encoding plasma membrane ATPase, phosphoglycerate kinase gene , ammonium transporter protein gene , cellulose synthase gene , and growth hormone response family gene were significantly upregulated.
DISCUSSION
It is hypothesized that the pro-growth mechanism of strain DGL1 in oats is the result of the coordination of multiple pathways through the promotion of oat energy metabolism, phytohormone signaling, secondary metabolite synthesis, and amino acid metabolism.
PubMed: 38633698
DOI: 10.3389/fmicb.2024.1321989 -
Journal of Proteome Research May 2024The delay in making a correct diagnosis of causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive...
The delay in making a correct diagnosis of causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies. In this study, immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of and by and were carried out, and the obtained sera were used to study their immunoreactivity against proteins. The results showed higher virulence, in terms of infection signs, weight loss, and histopathological damage, of the non-aggregative isolate. Moreover, was less virulent than but more than . Regarding the immunoproteomics study, 13 spots recognized by sera from mice infected with both phenotypes and analyzed by mass spectrometry corresponded to enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase. These four proteins were also recognized by sera obtained from human patients with disseminated infection but not by sera obtained from mice infected with or . Spot identification data are available via ProteomeXchange with the identifier PXD049077. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for .
Topics: Animals; Mice; Candida; Humans; Candidiasis; Immunoglobulin G; Antigens, Fungal; Proteomics; Candida albicans; Fungal Proteins; Phosphoglycerate Mutase; Phosphoglycerate Kinase; Glyceraldehyde-3-Phosphate Dehydrogenases; Antibodies, Fungal; Female; Virulence
PubMed: 38572994
DOI: 10.1021/acs.jproteome.3c00752 -
Frontiers in Bioscience (Landmark... Mar 2024Phosphoglycerate kinase 1 (PGK1) serves as a pivotal enzyme in the cellular glycolysis pathway, facilitating adenosine-triphosphate (ATP) production in tumor cells and... (Review)
Review
Phosphoglycerate kinase 1 (PGK1) serves as a pivotal enzyme in the cellular glycolysis pathway, facilitating adenosine-triphosphate (ATP) production in tumor cells and driving the Warburg effect. PGK1 generates ATP through the reversible phosphorylation reaction of 1,3-bisphosphoglycerate (1,3-BPG) to Mg-adenosine-5'-diphosphate (Mg-ADP). In addition to its role in regulating cellular metabolism, PGK1 plays a pivotal role in autophagy induction, regulation of the tricarboxylic acid cycle (TCA), and various mechanisms including tumor cell drug resistance, and so on. Given its multifaceted functions within cells, the involvement of PGK1 in many types of cancer, including breast cancer, astrocytoma, metastatic colon cancer, and pancreatic ductal adenocarcinoma, is intricate. Notably, PGK1 can function as an intracellular protein kinase to coordinate tumor growth, migration, and invasion via posttranslational modifications (PTMs). Furthermore, elevated expression levels of PGK1 have been observed in cancer tissues, indicating its association with unfavorable treatment outcomes and prognosis. This review provides a comprehensive summary of PGK1's expression pattern, structural features, functional properties, involvement in PTMs, and interaction with tumors. Additionally highlighted are the prospects for developing and applying related inhibitors that confirm the indispensable value of PGK1 in tumor progression.
Topics: Humans; Adenosine; Adenosine Triphosphate; Cell Line, Tumor; Colonic Neoplasms; Phosphoglycerate Kinase; Phosphorylation
PubMed: 38538272
DOI: 10.31083/j.fbl2903092 -
Antibiotics (Basel, Switzerland) Feb 2024Previously, we reported that metronidazole MICs are not dependent on the expression levels of genes in strains and we compared the proteomes of metronidazole-resistant...
Previously, we reported that metronidazole MICs are not dependent on the expression levels of genes in strains and we compared the proteomes of metronidazole-resistant laboratory strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical gene-positive and -negative strains to their metronidazole MICs. Metronidazole MICs were correlated with the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and (GCN5-like acetyltransferase), and (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in . This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion-complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified.
PubMed: 38534642
DOI: 10.3390/antibiotics13030207 -
Science Bulletin Feb 2024Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we...
Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2) progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1 (Pgk1) by repressing histone H3K27ac at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.
PubMed: 38493069
DOI: 10.1016/j.scib.2024.02.036 -
Journal of Translational Medicine Mar 2024Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric...
BACKGROUND
Circular RNAs (circRNAs) have been proved to play crucial roles in the development of various cancers. However, the molecular mechanism of circGLIS3 involved in gastric cancer (GC) tumorigenesis has not been elucidated.
METHODS
The higher expression level of circGLIS3 was identified in GC through RNA sequencing and subsequent tissue verification using Quantitative real-time PCR (qRT-PCR). A series of functional experiments in vitro and in vivo were performed to evaluated the effects of circGLIS3 on tumor growth and metastasis in GC. The interaction and regulation of circGLIS3/miR-1343-3p/PGK1 axis was confirmed by RNA pulldown, western blot, and rescue experiments. RIP and western blot were performed to demonstrate the role of circGLIS3 in regulating phosphorylation of VIMENTIN. We then used qRT-PCR and co culture system to trace circGLIS3 transmission via exosomal communication and identify the effect of exosomal circGLIS3 on gastric cancer and macrophages. Finally, RIP experiments were used to determine that EIF4A3 regulates circGLIS3 expression.
RESULTS
CircGLIS3(hsa_circ_0002874) was significantly upregulated in GC tissues and high circGLIS3 expression was associated with advanced TNM stage and lymph node metastasis in GC patients. We discovered that overexpression of circGLIS3 promoted GC cell proliferation, migration, invasion in vitro and in vivo, while suppression of circGLIS3 exhibited the opposite effect. Mechanistically, circGLIS3 could sponge miR-1343-3p and up-regulate the expression of PGK1 to promote GC tumorigenesis. We also found that circGLIS3 reduced the phosphorylation of VIMENTIN at ser 83 site by binding with VIMENTIN. Moreover, it was proven that exosomal circGLIS3 could promote gastric cancer metastasis and the M2 type polarization of macrophages. In the final step, the mechanism of EIF4A3 regulating the generation of circGLIS3 was determined.
CONCLUSION
Our findings demonstrate that circGLIS3 promotes GC progression through sponging miR-1343-3p and regulating VIMENTIN phosphorylation. CircGLIS3 is a potential therapeutic target for GC patients.
Topics: Humans; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; DEAD-box RNA Helicases; Eukaryotic Initiation Factor-4A; Gene Expression Regulation, Neoplastic; MicroRNAs; Phosphoglycerate Kinase; Phosphorylation; Stomach Neoplasms; Vimentin
PubMed: 38459513
DOI: 10.1186/s12967-023-04625-2 -
MBio Apr 2024Liquid-liquid phase separation (LLPS) plays a crucial role in various biological processes in eukaryotic organisms, including immune responses in mammals. However, the...
UNLABELLED
Liquid-liquid phase separation (LLPS) plays a crucial role in various biological processes in eukaryotic organisms, including immune responses in mammals. However, the specific function of LLPS in immune responses in remains poorly understood. Cactin, a highly conserved protein in eukaryotes, is involved in a non-canonical signaling pathway associated with Nuclear factor-κB (NF-κB)-related pathways in . In this study, we investigated the role of Cactin in LLPS and its implications for immune response modulation. We discovered that Cactin undergoes LLPS, forming droplet-like particles, primarily mediated by its intrinsically disordered region (IDR). Utilizing immunoprecipitation and mass spectrometry analysis, we identified two phosphorylation sites at serine residues 99 and 104 within the IDR1 domain of Cactin. Co-immunoprecipitation and mass spectrometry further revealed phosphoglycerate kinase (PGK) as a Cactin-interacting protein responsible for regulating its phosphorylation. Phosphorylation of Cactin by PGK induced a transition from stable aggregates to dynamic liquid droplets, enhancing its ability to interact with other components in the cellular environment. Overexpression of PGK inhibited C virus (DCV) replication, while PGK knockdown increased replication. DCV infection also increased Cactin phosphorylation. We also found that phosphorylation enhances the antiviral ability of Cactin by promoting liquid-phase droplet formation. These findings demonstrate the role of Cactin-phase separation in regulating DCV replication and highlight the modulation of its antiviral function through phosphorylation, providing insights into the interplay between LLPS and antiviral defense mechanisms.
IMPORTANCE
Liquid-liquid phase separation (LLPS) plays an integral role in various biological processes in eukaryotic organisms. Although several studies have highlighted its crucial role in modulating immune responses in mammals, its function in immune responses in remains poorly understood. Our study investigated the role of Cactin in LLPS and its implications for immune response modulation. We identified that phosphoglycerate kinase (PGK), an essential enzyme in the glycolytic pathway, phosphorylates Cactin, facilitating its transition from a relatively stable aggregated state to a more dynamic liquid droplet phase during the phase separation process. This transformation allows Cactin to rapidly interact with other cellular components, enhancing its antiviral properties and ultimately inhibiting virus replication. These findings expand our understanding of the role of LLPS in the antiviral defense mechanism, shedding light on the intricate mechanisms underlying immune responses in .
Topics: Animals; Carrier Proteins; Drosophila; Drosophila melanogaster; Drosophila Proteins; Phase Separation; Phosphoglycerate Kinase; Phosphorylation
PubMed: 38446061
DOI: 10.1128/mbio.01378-23 -
Cell Death & Disease Feb 2024Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle,...
Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle, which is called the Warburg effect. However, the detailed mechanisms of abnormal activation of the glycolysis pathway in colorectal cancer are largely unknown. In this study, we reveal that the protein arginine methyltransferase 1 (PRMT1) promotes glycolysis, proliferation, and tumorigenesis in CRC cells. Mechanistically, PRMT1-mediated arginine asymmetric dimethylation modification of phosphoglycerate kinase 1 (PGK1, the first ATP-producing enzyme in glycolysis) at R206 (meR206-PGK1) enhances the phosphorylation level of PGK1 at S203 (pS203-PGK1), which inhibits mitochondrial function and promotes glycolysis. We found that PRMT1 and meR206-PGK1 expression were positively correlated with pS203-PGK1 expression in tissues from colorectal cancer patients. Furthermore, we also confirmed that meR206-PGK1 expression is positively correlated with the poor survival of patients with colorectal cancer. Our findings show that PRMT1 and meR206-PGK1 may become promising predictive biomarkers for the prognosis of patients with CRC and that arginine methyltransferase inhibitors have great potential in colorectal cancer treatment.
Topics: Humans; Phosphoglycerate Kinase; Arginine; Cell Line, Tumor; Carcinogenesis; Cell Transformation, Neoplastic; Methylation; Colorectal Neoplasms; Glycolysis; Protein-Arginine N-Methyltransferases; Repressor Proteins
PubMed: 38402202
DOI: 10.1038/s41419-024-06544-6 -
Genes Feb 2024L. is an economically valuable plant with tolerance to drought and salinity. Its leaves are utilized in tea production and pharmaceuticals, while the stem bark serves...
L. is an economically valuable plant with tolerance to drought and salinity. Its leaves are utilized in tea production and pharmaceuticals, while the stem bark serves as a high-quality fiber material. To gain insights into the gene expression patterns of using quantitative real-time PCR (qRT-PCR), it is crucial to identify appropriate reference genes. This study selected nine candidate genes, including α-tubulin (), β-tubulin (), actin (), cyclophilin (), elongation factor-1α (), the B family of regulatory subunits of protein phosphatase (, , and ), and phosphoglycerate kinase (), to determine the most appropriate reference genes in the leaf, stem, and root tissues of . A comprehensive ranking by geNorm, NormFinder, BestKeeper, and RefFinder software and Venn diagrams was used to screen more stable reference genes in different tissues. The two most stable reference genes were and in leaves, and in stems, and and in roots, respectively. The relative expression values of the four genes involved in proline metabolism under polyethylene glycol treatment were used to validate the screened reference genes, and they exhibited highly stable expression levels. These findings represent the first set of stable reference genes for future gene expression studies in . They significantly contribute to enhancing the accuracy and reliability of gene expression analyses in this economically important plant species.
Topics: Real-Time Polymerase Chain Reaction; Peptide Elongation Factor 1; Apocynum; Reproducibility of Results; Genes, Plant
PubMed: 38397220
DOI: 10.3390/genes15020231