Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

Yang, Haojie; Jiang, Jing‐Hang; Yang, Yuting; Yang, Xiang-Di; Guo, Zhe; Qi, Yinliang; Zeng, Fenghua; Zhang, Kelan; Chen, Neng-Zhi; Xiang, Bang‐De; Li, Le‐Qun

doi:10.3748/wjg.v22.i39.8798

Cited by 13 publications

(12 citation statements)

References 32 publications

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“…Standard metabolic processes are adapted in cancer cells compared with normal cells in order to maintain their rapid proliferation and progression, and PKM2 serves an important role in cancer cell metabolism (18,19). It has previously been reported that cOX-2 is overexpressed in a number of tumor types, including Hcc (26). However, whether cOX-2 overexpression affects tumor cells metabolism via regulating PKM2 is currently unclear.…”

Section: Discussionmentioning

confidence: 99%

COX-2 induces apoptosis-resistance in hepatocellular carcinoma cells via the HIF-1α/PKM2 pathway

Wang

Fan

et al. 2018

Int J Mol Med

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The pyruvate kinase M2 isoform (PKM2) is a key component of aerobic glycolysis and has been reported to regulate apoptosis. However, it is unclear whether PKM2 is involved in cyclooxygenase-2 (cOX-2) induced apoptosis-resistance in hepatocellular carcinoma (Hcc) cells. In the present study, it was observed that cOX-2 and PKM2 were significantly elevated in hepatocellular carcinoma tissues compared with adjacent liver tissues (P<0.05). Furthermore, their expression was positively associated with worse clinicopathological characteristics, which indicates poor prognosis in patients with HCC. COX-2 knockdown significantly reduced the expression of PKM2 and hypoxia inducible factor-1α (HIF-1α) at the mRNA and protein levels in addition to inhibiting proliferation (P<0.05), whereas apoptosis was notably increased. Furthermore, HIF-1α and PKM2-knockdown increased cell apoptosis without inhibiting cOX-2 expression. PKM2 inhibition did not have a marked effect on cOX-2 and HIF-1α expression. In conclusion, the results of the present study suggested that HIF-1α/PKM2 pathway-associated metabolic changes may facilitate cOX-2-induced apoptosis resistance in Hcc cells.

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Section: Discussionmentioning

confidence: 99%

COX-2 induces apoptosis-resistance in hepatocellular carcinoma cells via the HIF-1α/PKM2 pathway

Wang

Fan

et al. 2018

Int J Mol Med

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“…Second, COX-2 demonstrates high expression in HCC and can promote tumor initiation, differentiation, invasion, and metastasis. 16 , 47 , 48 A meta-analysis with 11 publications further indicates that high expression of COX-2 is associated with decreased survival and worse prognosis in HCC. 49 In addition, it is suggested that COX-1 plays a similar role, and COX-1 inhibitors may show potential therapeutic implications in HCC.…”

Section: Discussionmentioning

confidence: 99%

The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent risk of hepatocellular carcinoma: a meta-analysis

Pang¹,

Jin²,

Qu³

et al. 2017

OTT

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BackgroundRecent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial.MethodsTo assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications.ResultsA total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR =0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06).ConclusionTaken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC.

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“…PTGS2 is a proinflammatory enzyme induced by prostaglandins involved in cell proliferation, tumorigenesis, progression, and metastasis[ 25 ] . The PTGS2 gene is commonly up-regulated and plays a role in apoptosis and proliferation of cells in numerous types of cancers[ 26 , 27 ]. It is noteworthy that one meta-analysis showed that the HCC susceptibility is associated with a PTGS2 variant[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

Liang¹,

Wang²,

Xu³

et al. 2018

WJG

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AIMTo discover methylated-differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC) and to explore relevant hub genes and potential pathways.METHODSThe data of expression profiling GSE25097 and methylation profiling GSE57956 were gained from GEO Datasets. We analyzed the differentially methylated genes and differentially expressed genes online using GEO2R. Functional and enrichment analyses of MDEGs were conducted using the DAVID database. A protein-protein interaction (PPI) network was performed by STRING and then visualized in Cytoscape. Hub genes were ranked by cytoHubba, and a module analysis of the PPI network was conducted by MCODE in Cytoscape software.RESULTSIn total, we categorized 266 genes as hypermethylated, lowly expressed genes (Hyper-LGs) referring to endogenous and hormone stimulus, cell surface receptor linked signal transduction and behavior. In addition, 161 genes were labelled as hypomethylated, highly expressed genes (Hypo-HGs) referring to DNA replication and metabolic process, cell cycle and division. Pathway analysis illustrated that Hyper-LGs were enriched in cancer, Wnt, and chemokine signalling pathways, while Hypo-HGs were related to cell cycle and steroid hormone biosynthesis pathways. Based on PPI networks, PTGS2, PIK3CD, CXCL1, ESR1, and MMP2 were identified as hub genes for Hyper-LGs, and CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10 were hub genes for Hypo-HGs by combining six ranked methods of cytoHubba.CONCLUSIONIn the study, we disclose numerous novel genetic and epigenetic regulations and offer a vital molecular groundwork to understand the pathogenesis of HCC. Hub genes, including PTGS2, PIK3CD, CXCL1, ESR1, MMP2, CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10, can be used as biomarkers based on aberrant methylation for the accurate diagnosis and treatment of HCC.

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Cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

Cited by 13 publications

References 32 publications

COX-2 induces apoptosis-resistance in hepatocellular carcinoma cells via the HIF-1α/PKM2 pathway

COX-2 induces apoptosis-resistance in hepatocellular carcinoma cells via the HIF-1α/PKM2 pathway

The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent risk of hepatocellular carcinoma: a meta-analysis

Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

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