Melatonin inhibited tumorigenesis of bladder cancer via suppressing PPARγ/ENO1 mediated glycolysis
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ABSTRACT:
PROVIDER: PRJNA876233 | ENA |
REPOSITORIES: ENA
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Project description:Bladder cancer (BLCA) is one of the most malignant human cancers in the world. The increasingly prominent phenomenon of chemoresistance has become an essential obstacle to clinical treatment for BLCA, and there is an urgent need to explore novel drugs to improve the current clinical status. Melatonin is a well-known natural hormone that showed a potential anti-cancer effect in multiple human cancers. In our study, we comprehensively explored the inhibitory effect of melatonin on BLCA and found that it could suppress the glycolysis process in BLCA cells. Moreover, we discovered that the ninth step enzyme ENO1 of glycolysis was the downstream effector of melatonin and could be a predictive biomarker of BLCA patients.
2022-09-06 | GSE212599 | GEO
Project description:Melatonin is a well-known natural hormone, which shows a potential anticancer effect in many human cancers. Bladder cancer (BLCA) is one of the most malignant human cancers in the world. Chemoresistance is an increasingly prominent phenomenon that presents an obstacle to the clinical treatment of BLCA. There is an urgent need to investigate novel drugs to improve the current clinical status. In our study, we comprehensively explored the inhibitory effect of melatonin on BLCA and found that it could suppress glycolysis process. Moreover, we discovered that ENO1, a glycolytic enzyme involved in the ninth step of glycolysis, was the downstream effector of melatonin and could be a predictive biomarker of BLCA. We also proved that enhanced glycolysis simulated by adding exogenous pyruvate could induce gemcitabine resistance, and melatonin treatment or silencing of ENO1 could intensify the cytotoxic effect of gemcitabine on BLCA cells. Excessive accumulation of reactive oxygen species (ROS) mediated the inhibitory effect of melatonin on BLCA cells. Additionally, we uncovered that PPARγ was a novel upstream regulator of ENO1, which mediated the downregulation of ENO1 caused by melatonin. Our study offers a fresh perspective on the anticancer effect of melatonin and encourages further studies on clinical chemoresistance.
| S-EPMC10079981 | biostudies-literature
Project description:The essential roles of PCNA as a scaffold protein in DNA replication and repair are well established, while its more recently discovered cytosolic roles are less explored. Alpha-enolase (ENO1) and 6-phosphogluconate dehydrogenase (6PGD), important proteins in glycolysis and the Pentose Phosphate Pathway (PPP), respectively, both contain PCNA interacting motifs. Here we show reduced binding to PCNA when the PCNA interacting motif APIM in ENO1 is mutated. Mutant cells have lower ENO1 protein levels, have reduced glucose consumption, altered glycolytic metabolite and nucleoside phosphate pools and increased activation of the citric acid cycle (TCA) compared to parental cells. Treatment of a panel of haematological cell lines with a cell penetrating peptide containing APIM (ATX-101), lead to a metabolic shift with reduction in glycolytic metabolite and nucleoside phosphate pools as well reduced levels of ENO1 and 6PGD proteins. These results suggests that PCNA stabilize ENO1 and 6PGD, and that targeting PCNA reduce the glycolysis, PPP and nucleoside phosphate pools via destabilization of these proteins.
2023-03-10 | PXD028314 | Pride
Project description:Hypertrophic scar (HS) is a fibrotic skin condition and characterized by abnormal proliferation of myofibroblasts and accumulation of extracellular matrix. Melatonin, an endogenous hormone, can alleviate fibrosis in multiple models of diseases. This study examined the effect of melatonin on fibrosis in primary fibroblasts from human HS (HSFs) and a rabbit ear model and potential mechanisms. Melatonin treatment significantly decreased the migration and contraction capacity, collagen and α-smooth muscle actin (α-SMA) production in HSFs. RNA-sequencing and bioinformatic analyses indicated that melatonin modulated the expression of genes involved in autophagy and oxidative stress. Mechanistically, melatonin treatment attenuated the AKT/mTOR activation through affecting the binding of MT2 receptor with PI3K to enhance autophagy, decreasing fibrogenic factor production in HSFs. Moreover, melatonin treatment inhibited HS formation in rabbit ears by enhancing autophagy. The anti-fibrotic effects of melatonin were abrogated by treatment with an autophagy inhibitor (3-methyladenine, 3-MA), an Akt activator (SC79), or an MT2 selective antagonist (4-phenyl-2propionamidotetralin, 4-P-PDOT). Therefore, melatonin may be a potential drug for prevention and treatment of HS.
2022-06-03 | GSE190135 | GEO
Project description:Enolase 1 (ENO1) is a glycolytic enzyme that plays essential roles in various pathological activities including cancer development. However, the mechanisms underlying ENO1-contributed tumorigenesis are not well explained. Here, we uncover that ENO1, as an RNA-binding protein, binds to the cytosine-uracil-guanine-rich elements of YAP1 messenger RNA to promote its translation. ENO1 and YAP1 positively regulate alternative arachidonic acid (AA) metabolism by inverse regulation of PLCB1 and HPGD (15-hydroxyprostaglandin dehydrogenase). The YAP1/PLCB1/HPGD axis-mediated activation of AA metabolism and subsequent accumulation of prostaglandin E2 (PGE2) are responsible for ENO1-mediated cancer progression, which can be retarded by aspirin. Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.
2023-05-19 | GSE183703 | GEO
Project description:HeLa cells were either treated with ENO1 or control siRNAs using the protocol of the RNAiMax reagent (ENO1 pool: SMARTpool ON-TARGETplus L-004034-00-0005 and control pool: ON-TARGETplus non-targeting siRNAs 1-4). Three replicates per condition were produced.
2020-10-27 | E-MTAB-9032 | biostudies-arrayexpress
Project description:The loss of PPARγ is found to be associated with the development of pulmonary hypertension (PH). We hypothesize that PPARγ inhibition induced gene expression changes may underscore the endothelial dysfunction in the disease process. We utilized microarray analysis to determine gene expression changes in PPARγ inhibited ovine PAECs. Ovine PAECs were treated with vehicle (DMSO) or GW9662 (5μM) for 24hrs, and total RNA was extracted for microarray analysis.
2009-12-27 | E-GEOD-14546 | biostudies-arrayexpress
Project description:Chromatin immunoprecipitation-Sequence (ChIP-Seq) analysis indicated increased binding of PPARγ to Srebf1 promoter region after activating iNKT cells, and that was inhibited by T007—PPARγ inhibitor .
2021-05-31 | GSE131908 | GEO
Project description:ENO1 (α-Enolase 1) is a key glycolytic enzyme that catalyzes the dehydratation of 2-phosphoglycerate to phosphoenolpyruvate. It also belongs to a member of the RNA degradosome of Escherichia coli and facilitates RNA degradation, but it’s currently unknown whether ENO1 possesses similar function in eukaryotes. To test this possibility,we performed RNA-seq assays expressing NTC or ENO1 shRNA, respectively.
2021-09-10 | GSE153989 | GEO
Project description:Melatonin is a well-known agent that plays multiple roles in animals. Its possible function in plants is less clear. In the present study, we tested the effect of melatonin (N-acetyl-5-methoxytryptamine) on soybean growth and development. Both spraying of leaves and seed-coating with melatonin significantly promoted soybean growth as judged from leaf size and plant height. This enhancement was also observed in soybean production and their fatty acid content. Melatonin increased pod number, seed number and seed weight. However, the 100-seed weight was not influenced by melatonin application. Melatonin also improved soybean tolerance to salt and drought stresses. Transcriptome analysis revealed that melatonin up-regulated the expression of many genes and alleviated the inhibitory effects of salt stress on gene expressions. Further detailed analysis of the affected pathways documents that melatonin likely achieved its promotional roles in soybean through enhancement of genes involved in cell division, photosynthesis, carbohydrate metabolism, fatty acid biosynthesis and ascorbate metabolism. Our results demonstrate that melatonin has significant potential for improving of soybean growth and seed production. Further study should uncover more about the molecular mechanisms of melatoninM-bM-^@M-^Ys function in soybeans and other crops. Four different treatments were chosen, water, salt, 100M-BM-5M melatonin and salt plus 100M-BM-5M melatonin. The comparison of salt/melatonin-treated sample versus water-treated sample reveals salt or melatonin induced transcriptome changes. The comparison of melatonin plus salt treated sample versus salt-treated sample reveals melatonin induced changes when salt exists.
2014-08-31 | E-GEOD-57960 | biostudies-arrayexpress