Peroxisome proliferator‐activated receptor γ upregulates galectin‐9 and predicts prognosis in intestinal‐type gastric cancer

Cho, Soo‐Jeong; Kook, Myeong Cherl; Lee, Jun Ho; Shin, Ji Young; Park, Juri; Bae, Young Ki; Choi, Il Ju; Ryu, Keun Won; Kim, Young Woo

doi:10.1002/ijc.29056

Cited by 31 publications

(26 citation statements)

References 47 publications

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“…In the present study, the downregulated DEGs were significantly enriched in ‘chemical carcinogenesis’, ‘metabolism of xeno-biotics by cytochrome P450’, ‘peroxisome’, ‘fatty acid degradation’ and ‘gastric acid secretion’. These results also coincided with the results of previous studies ( 23 – 27 ).…”

Section: Discussionsupporting

confidence: 93%

Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis

Sun

Liu

et al. 2018

Mol Med Report

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Gastric cancer has become a serious disease in the past decade. It has the second highest mortality rate among the four most common cancer types, leading to ~700,000 mortalities annually. Previous studies have attempted to elucidate the underlying biological mechanisms of gastric cancer. The present study aimed to obtain useful biomarkers and to improve the understanding of gastric cancer mechanisms at the genetic level. The present study used bioinformatics analysis to identify 1,829 differentially expressed genes (DEGs) which were obtained from the GSE54129 dataset. Using protein-protein interaction information from the Search Tool for the Retrieval of Interacting Genes database, disease modules were constructed for gastric cancer using Cytoscape software. In the Gene Ontology analysis of biology processes, upregulated genes were significantly enriched in ‘extracellular matrix organization’, ‘cell adhesion’ and ‘inflammatory response’, whereas downregulated DEGs were significantly enriched in ‘xenobiotic metabolic process’, ‘oxidation-reduction process’ and ‘steroid metabolic process’. During Kyoto Encyclopedia of Genes and Genomes analysis, upregulated DEGs were significantly enriched in ‘extracellular matrix-receptor interaction’, ‘focal adhesion’ and ‘PI3K-Akt signaling pathway’, whereas the downregulated DEGs were significantly enriched in ‘chemical carcinogenesis’, ‘metabolism of xenobiotics by cytochrome P450’ and ‘peroxisome’. The present study additionally identified 10 hub genes from the DEGs: Tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), tetraspanin 4 (TSPAN4), lysophosphatidic acid receptor 2 (LPAR2), adenylate cyclase 3 (ADCY3), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), neuromedin U (NMU), C-X-C motif chemokine ligand (CXCL12), fos proto-oncogene, AP-1 transcription factor subunit (FOS) and sphingosine-1-phosphate receptor 1 (S1PR1), which have high degrees with other DEGs. The survival analysis revealed that the high expression of ADCY3, LPAR2, S1PR1, TP53 and TSPAN4 was associated with a lower survival rate, whereas high expression of CXCL8, FOS, NMU and PIK3R1 was associated with a higher survival rate. No significant association was identified between CXCL12 and survival rate. Additionally, TSPAN1 and TSPAN8 appeared in the top 100 DEGs. Finally, it was observed that 4 hub genes were highly expressed in gastric cancer tissue compared with para-carcinoma tissue in the 12 patients; the increased TSPAN4 was significant (>5-fold). Tetraspanin family genes may be novel biomarkers of gastric cancer. The findings of the present study may improve the understanding of the molecular mechanisms underlying the development of gastric cancer.

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Section: Discussionsupporting

confidence: 93%

Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis

Sun

Liu

et al. 2018

Mol Med Report

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“…Rosiglitazone, a PPAR γ agonist was shown to inhibit hepatocellular carcinoma (32) , and gastric cancer cell growth (33). Also, troglitazone the other PPAR γ agonist has the same effect on prostate cancer cells (34).…”

Section: Discussionmentioning

confidence: 99%

PPAR γ agonist, pioglitazone, suppresses melanoma cancer in mice by inhibiting TLR4 signaling

2019

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Background: Although previous studies demonstrated an anticancer effect for the ligands of peroxisome proliferator-activated receptor gamma (PPARγ) through activation of its anti-inflammatory responses, nevertheless the anti-tumor mechanism of PPARγ has not been intensively investigated. One of the molecules involved in cancer progression is toll-like receptor 4 (TLR4).Methods: B16F10 melanoma cells were cultured with or without LPS for 24 hr. The cells were subcutaneously injected to two groups of C57BL/6 mice. After the development of palpable tumors each group of animals were divide to four sub-groups and received pioglitazone in different dose ranges (0,10,50,100 mg/kg/day) for 10 days. At the end of the study, the expression of Tlr4, Myd-88, Nf-kb1 genes was evaluated by qRT-PCR in different groups in mice tumor. The TLR-4 protein expression was evaluated by IHC. TNF-α level in mice tumor and serum were measured by ELISA kits. Tumor volume was measured with Vernier calipers.Results: We observed that activation of PPARγ by its agonist, pioglitazone, reduces tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA expression, TLR4 protein expression and TNF-α production in melanoma tumor especially in groups that were injected with LPS –stimulated cells. Moreover, treatment of melanoma cells with pioglitazone showed that the inhibitory effects of pioglitazone on LPS-induced inflammatory responses were TLR4 dependent.Conclusions: The results indicate that pioglitazone, a PPARγ agonist, has a beneficial protective effect against melanoma via interfering with the TLR4-dependent signaling pathways.

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“…Though the roles of PPARγ in cancer therapy are debatable, accumulating evidence suggested that activation of PPARγ by agonists exerts an inhibitory effect on cancer cells [32]. For example, PPARγ agonists dramatically reduced cell growth of hepatocellular carcinoma [33], prostate cancer [34], and gastric cancer [35] via regulating the expression and blocking the oncogenic proteins. In our study, we found that PPARγ agonist RGZ had an ability to inhibit proliferation of esophageal cancer cells in time- and dose-dependent manners.…”

Section: Discussionmentioning

confidence: 99%

Activation of PPARγ suppresses proliferation and induces apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway

Yang

Liu

et al. 2016

Oncotarget

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Although substantial studies on peroxisome proliferator-activated receptor γ (PPARγ) have focused on the mechanisms by which PPARγ regulates glucose and lipid metabolism, recent reports have suggested that PPARγ shows tumorigenic or antitumorigenic effects. The roles and mechanisms of PPARγ activation in esophageal cancer remain unclarified. EC109 and TE10 esophageal cancer cells were treated with 0, 10, 20 and 40 mM of PPARγ agonist rosiglitazone (RGZ) for 24, 48, and 72 h, and the cell viability and apoptosis were detected using methyl thiazolyl tetrazolium (MTT) assay and Flow cytometric (FCM) analysis, respectively. Moreover, the effects of inhibition of PPARγ by antagonist or specific RNA interference on cell viability, apoptosis, the Toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) pathways were evaluated. Additionally, the effect of TLR4 signaling on the MAPK pathway, cell viability and apoptosis was assessed. The results showed that RGZ suppressed proliferation and induced apoptosis of esophageal cancer cells, which could be partly restored by inactivation of PPARγ. RGZ suppressed the MAPK and TLR4 pathways, and the inhibitory effect could be counteracted by PPARγ antagonist or specific RNA interference. We also suggested that MAPK activation was regulated by the TLR4 pathway and that blocking the TLR4 and MAPK pathways significantly suppressed proliferation and induced apoptosis of esophageal cancer cells. In conclusion, our data suggested that activation of PPARγ suppressed proliferation and induced apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway.

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Peroxisome proliferator‐activated receptor γ upregulates galectin‐9 and predicts prognosis in intestinal‐type gastric cancer

Cited by 31 publications

References 47 publications

Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis

Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis

PPAR γ agonist, pioglitazone, suppresses melanoma cancer in mice by inhibiting TLR4 signaling

Activation of PPARγ suppresses proliferation and induces apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway

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