Prognostic and immunological significance of peroxisome proliferator-activated receptor gamma in hepatocellular carcinoma based on multiple databases
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Peroxisome proliferator-activated receptor gamma (PPARG) plays some roles in preventing liver disease progression to hepatocellular carcinoma. However, there is limited information about the function of PPARG of in hepatocellular carcinoma. This study aimed to determine the significance of PPARG in immunological response and as a biomarker for hepatocellular carcinoma survival.We investigated the expression, prognosis, Kyoto Encyclopedia of Genes and Genomes/Gene Ontology biological process enrichment, and immune significance of PPARG using data from three databases-The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus-through bioinformatics analysis as well as experimental verification in proliferation function of PPARG in HepG2 cell.High PPARG expression in hepatocellular carcinoma tissues positively correlated with TP53 mutation, and predicted poor prognosis. The results of enrichment and immune infiltration showed that PPARG negatively correlated with the complement system and macrophage infiltration, and laboratory results support that PPARG regulate proliferation of HepG2 cell.PPARG is upregulated in hepatocellular carcinoma and it correlates with a worse prognosis. Moreover, PPARG may play an important role in the cell proliferation, complement system and immune cell infiltration in hepatocellular carcinoma.Hepatic stellate cell
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Peroxisome proliferator
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Peroxisome proliferator
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Peroxisome proliferator-activated receptors (PPARs) are members of nuclear transcription factors. The functions of the PPAR family (PPARA, PPARD, and PPARG) and their coactivators (PPARGC1A and PPARGC1B) in maintenance of lipid and glucose homeostasis have been unveiled. However, the roles of PPARs in cancer development remain elusive. In this work, we made use of 11,057 samples across 33 TCGA tumor types to analyze the relationship between PPAR transcriptional expression and tumorigenesis as well as drug sensitivity. We performed multidimensional analyses on PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B, including differential expression analysis in pan-cancer, immune subtype analysis, clinical analysis, tumor purity analysis, stemness correlation analysis, and drug responses. PPARs and their coactivators expressed differently in different types of cancers, in different immune subtypes. This analysis reveals various expression patterns of the PPAR family at a level of pan-cancer and provides new clues for the therapeutic strategies of cancer.
PPARGC1A
PPAR agonist
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Objective: The Angiotensin-II receptor blocker telmisartan and sulfonylurea glimepiride may have clinical usefulness as partial agonists of PPARg.We investigated additive and antagonistic effects among combinations of telmisartan, glimepiride, and the Thiazolidinedione (TZD) selective PPARg agonist pioglitazone on transcriptional activity of PPARg.Materials/Methods: The receptors of pCMX-PPARg and pCMX-RXR, and PPRE-Luc reporter gene were transfected into CV1 cells, and treated with following agents, and luciferace assay was performed.Moreover, mammalian two-hybrid assay was done using GAL4 responsive reporter tk-MH100(UAS)×4-Luc and the chimeric receptor GAL4-PPARg.Results: Telmisartan increased transactivation of PPARg dose dependently.Activation by telmisartan 10 µM was 58.8% of that by pioglitazone 10 µM.Glimepiride also increased transactivation of PPARg dose dependently.Activation by glimepiride 10 µM was 49.8% of that by pioglitazone 10 µM.Addition of telmisartan 5 µM significantly enhanced transactivation by glimepiride 10 and 50 µM.Moreover, addition of pioglitazone 0.5 µM significantly enhanced transactivation by glimepiride 10 and 50 µM.Mammalian two-hybrid assay showed additive effect between glimepiride and telmisartan on binding of SRC-1 to PPARg.On the other hand, addition of glimepiride 10 and 50 µM reduced transactivation by pioglitazone 5 µM to 74% and 70%, respectively.Conclusion: Partial agonists of PPARg additively enhanced transactivation by other agonists, whereas high concentration of partial agonists reduced transactivation by full agonist antagonistically.
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Rosiglitazone
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Peroxisome proliferator
Pancreatic Islets
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Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that regulate many physiological processes. Recent studies have implicated PPARs in the control of fibrosis. In particular, agonists of PPARg have been found to have antifibrotic effects on a number of tissues including the lung, heart, and liver. This antifibrotic effect is related to the inhibition of TGF-?/ Smad signal transduction including other pathways that still remain unidentified. This review focuses on PPARg and its mode of activation in relation to fibrosis.
PPAR agonist
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