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Enhanced aerobic glycolysis has been one of the cancer hallmarks. Cancerous cells develop certain alterations during glucose metabolism for supporting their infinite growth requirement and metastasis. Therefore, targeting metabolism, for instance, crucial glycolytic enzymes, will provide a novel therapeutic strategy to treat cancer. Aldolase B (ALDOB), as a glycolytic enzyme, plays a contentious role in cancers and can either act against the tumor or as an oncogenic enzyme. The precise role of ALDOB in gastric cancer (GC) and the endogenous process is elusive and needs further exploration. This investigation revealed that ALDOB expression was markedly decreased in GC tissues. Furthermore, ALDOB inhibition was notably linked with tumor size, depth of tumor invasion, lymph node metastasis (LNM), tumor node metastases (TNM) staging, and substandard prognosis of GC. The assessment of loss- and gain-of-function indicated that ALDOB inhibited the growth and the migrative ability of GC cells, suggesting its anti-tumor role. Mechanistic studies revealed that ALDOB modulates the AKT signaling pathway. The increase in growth and cells' ability to migrate stimulated by ALDOB inhibition was partially impaired in cells under the influence of AKT inhibitors. The overall data highlights a novel target, the ALDOB/AKT signaling axis for the treatment of GC.

ObjectiveGastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. However, mounting evidence indicates a link between the glycolysis and tumorigenesis, including gastric cancer.MethodsOur research identified 5508 differently expressed mRNAs in gastric cancer. Then, the genes highly associated with tumorigenesis were identified through weighted correlation network analysis (WGCNA). Bioinformatics analysis observed that these hub genes were significantly linked to the regulation of cell cycle, drug metabolism, and glycolysis. Among these hub genes, there is a critical gene involved in glycolysis regulation, namely fructose-bisphosphate B (ALDOB).ResultsAnalysis based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets revealed that ALDOB was significantly downregulated in GC compared with normal tissues. In addition, cell viability assay confirmed that ALDOB acted as a tumor suppressor. Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. Our results showed that the expression of ALDOB was significantly lower in GC tissues than in normal tissues. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.

: CD8 T cells undergo a series of metabolic reprogramming processes during their activation and proliferation, including increased glycolysis, decreased aerobic oxidation of sugars, increased amino acid metabolism and increased protein synthesis. However, it is still unclear what factors regulate these metabolic reprogramming processes in CD8 T cells in the tumor immune microenvironment. : T cell chromobox protein 4 (CBX4) knock-out mice models were used to determine the role of CBX4 in CD8 T cells on the tumor immune microenvironment and tumor progression. Flow cytometry, Cut-Tag qPCR, Chip-seq, immunoprecipitation, metabolite detection, lentivirus infection and adoptive T cells transfer were performed to explore the underlying mechanisms of CBX4 knock-out in promoting CD8+ T cell activation and inhibiting tumor growth. : We found that CBX4 expression was induced in tumor-infiltrating CD8 T cells and inhibited CD8 T cell function by regulating glucose metabolism in tumor tissue. Mechanistically, CBX4 increases the expression of the metabolism-associated molecule aldolase B (Aldob) through sumoylation of trans-acting transcription factor 1 (SP1) and Krüppel-like factor 3 (KLF3). In addition, Aldob inhibits glycolysis and ATP synthesis in T cells by reducing the phosphorylation of the serine/threonine protein kinase (Akt) and ultimately suppresses CD8 T cell function. Significantly, knocking out CBX4 may improve the efficacy of anti-PD-1 therapy by enhancing the function of CD8 T cells in the tumor microenvironment. : CBX4 is involved in CD8 T cell metabolic reprogramming and functional persistence in tumor tissues, and serves as an inhibitor in CD8 T cells' glycolysis and effector function.

Glycogen storage disease type Ia (GSDIa) is an inherited disorder of carbohydrate metabolism. Patients present with excessive storage of glycogen and fat in the liver and kidneys and are potentially at risk of developing long-term complications. Currently, the mainstay of treatment is highly tailored dietary regimens aimed at improving metabolic control. In the present study, to better elucidate the mechanisms potentially involved in the development of long-term complications, a mass spectrometry-based strategy was employed for an in-depth characterization of the serum proteomic and metabolomic profile of n.12 GSDIa patients. The detection of differential abundance of highly liver-specific circulating proteins and choline-related metabolites in patients provides new insights into the extent of liver damage and dysregulation of lipid metabolism in GSDIa. Specifically, the differential abundance of serum aldolase B and its positive correlation with traditional liver function markers supports its role as a potential biomarker for long-term monitoring of GSDIa liver injury.

The characterization of circulating tumor cells (CTCs) holds promises for precision medicine because these cells are an important clinical indicator of treatment efficacy. We established the first and still only nine permanent colon CTC lines from peripheral blood samples of a patient with metastatic colon cancer collected at different time points during treatment and cancer progression. The study objectives were ( i ) to compare the gene expression profiles of these CTC lines, and ( ii ) to determine the main features acquired during treatment. The number of upregulated genes was higher in the CTC lines obtained after treatment, indicating that they acquired properties to escape treatment pressure. Among these upregulated genes, some are involved in the mTOR and PI3K/AKT signaling pathways. Moreover, cytidine deaminase expression was significantly increased in the CTC lines obtained after failure of the first- and second-line 5-fluorouracile-based treatments, suggesting that these CTCs can eliminate this specific drug and resist to therapy. Several enzymes involved in xenobiotic metabolism also were upregulated after treatment, suggesting the activation of detoxification mechanisms in response to chemotherapy. Finally, the significant higher expression of aldolase B in four of the six CTC lines obtained after treatment withdrawal and cancer progression indicated that these clones originated from liver metastases. In conclusion, these CTC lines generated at different time points during treatment of metastatic colon cancer in a single patient are characterized by the deregulation of different genes that promote ( i ) drug resistance, ( ii ) xenobiotic and energy metabolism, and ( iii ) stem cell properties and plasticity.

Excess fructose intake is associated with obesity, fatty liver, tooth decay, cancer, and cardiovascular diseases. Even after the ingestion of fructose, fructose concentration in the portal blood is never high; fructose is further metabolized in the liver, and the blood fructose concentration is 1/100th of the glucose concentration. It was previously thought that fructose was metabolized in the liver and not in the small intestine, but it has been reported that metabolism in the small intestine also plays an important role in fructose metabolism. Glut5 knockout mice exhibit poor fructose absorption. In addition, endogenous fructose production via the polyol pathway has also received attention; gene deletion of aldose reductase (Ar), ketohexokinase (Khk), and triokinase (Tkfc) has been found to prevent the development of fructose-induced liver lipidosis. Carbohydrate response element-binding protein (Chrebp) regulates the expression of Glut5, Khk, aldolase b, and Tkfc. We review fructose metabolism with a focus on the roles of the glucose-activating transcription factor Chrebp, fructolysis, and the polyol pathway.

Background Microtia is reported to be one of the most common congenital craniofacial malformations. Due to the complex etiology and the ethical barrier of embryonic study, the precise mechanisms of microtia remain unclear. Here we report a rare case of microtia with costal chondrodysplasia based on bioinformatics analysis and further verifications on other sporadic microtia patients. Results One hundred fourteen deleterious insert and deletion (InDel) and 646 deleterious SNPs were screened out by WES, candidate genes were ranked in descending order according to their relative impact with microtia. Label-free proteomic analysis showed that proteins significantly different between the groups were related with oxidative stress and energy metabolism. By real-time PCR and immunohistochemistry, we further verified the candidate genes between other sporadic microtia and normal ear chondrocytes, which showed threonine aspartase, cadherin-13, aldolase B and adiponectin were significantly upregulated in mRNA levels but were significantly lower in protein levels. ROS detection and mitochondrial membrane potential (∆ Ψ m) detection proved that oxidative stress exists in microtia chondrocytes. Conclusions Our results not only spot new candidate genes by WES and label-free proteomics, but also speculate for the first time that metabolism and oxidative stress may disturb cartilage development and this might become therapeutic targets and potential biomarkers with clinical usefulness in the future.

Gastric cancer (GC) is a malignant tumor with high incidence rate. H3K9me3 is related to transcriptional suppression and modulated by histone methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39H1). SUV39H1 is dysregulated in assorted cancers and exerts the regulatory function. Nevertheless, the specific biofunction of SUV39H1 in GC needs further confirmation. SUV39H1 and H3K9me3 expressions were tested through RT-qPCR and western blot. Colony formation, wound healing, and transwell assays were employed for testing cell behaviors. ChIP assay was utilized for assessing the interaction between H3K9me3 and aldolase B (ALDOB). Xenograft experiment was employed for measuring tumor growth. We found that SUV39H1 and H3K9me3 were overexpressed in GC tissues and cells. SUV39H1 knockdown notably suppressed GC cell proliferative, migratory, and invasive capabilities. The treatment of chaetocin or F5446 (inhibitors of SUV39H1 enzymatic activity) also restrained GC cell behaviors. In addition, we discovered that SUV39H1 could negatively regulate ALDOB expression. SUV39H1 depletion reduced H3K9me3 modification to ALDOB promoter region. In rescue assays, we proved that ALDOB reduction reversed the inhibitory functions of SUV39H1 silencing on GC progression. Furthermore, tumor growth of mice was suppressed by sh-SUV39H1 transfection, chaetocin treatment, or F5446 treatment. In conclusion, SUV39H1 promoted GC progression by modulating the H3K9me3/ALDOB axis.

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.

Aldolase B ( ), functioning as a glycolytic enzyme, exhibits a controversial role in malignancies and demonstrates dual potential as both a tumor suppressor and cancer-promoting enzyme. Nevertheless, it is still uncertain if there is a relationship between levels, prognosis, and tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC). This study aims to investigate the prognostic significance of in ccRCC and its potential association with clinicopathological features and tumor immune microenvironment. By integrating multi-database bioinformatics analysis and experimental validation, we seek to elucidate the role of in ccRCC progression and its potential as a predictive biomarker. To ascertain the potential link between level, clinical parameters, and overall survival (OS) in individuals with ccRCC, we employed diverse databases, which include The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA) and The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN). Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and was carried out using the TIMER database. Immunohistochemistry (IHC) was applied to identify the level in a tissue microarray. The expression of demonstrated a strong association with pathologic T stage, pathologic N stage, pathologic M stage, histologic grade, and gender. Decreased level was linked to unfavorable disease-specific survival (DSS), progress free interval (PFI), and OS outcomes (  < 0.001). Subsequently, a marked link was observed between level and a heightened presence of infiltrating Treg, Th17 cells, and neutrophils in ccRCC. IHC showed that the level in ccRCC samples was notably diminished relative to that in the adjacent normal tissues. As a prospective predictive indicator for individuals with ccRCC, reduced level exhibited strong correlations with clinical characteristics, unfavorable outcomes, and immune infiltration in individuals with ccRCC.