Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway

Xu, Ting; Wu, Sihai; Yuan, Yuan; Yan, Gen; Xiao, Dajiang

doi:10.3892/ol.2014.2422

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…In the present study, PDE4D silencing attenuated migration and invasion abilities of PDAC cells and decreased β-catenin level simultaneously. Previous studies have reported that knockdown of PDE4D resulted in EGFR/PI3K/AKT signaling inactivation in nasopharyngeal carcinoma cells 37. And EGF/AKT could contribute to phosphorylation of β-catenin and increased its protein level in cancer cells, therefore, enhanced β-catenin downstream transcriptional activity 38, 39.…”

Section: Discussionmentioning

confidence: 95%

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma

Liu¹,

Ma²,

Wang³

et al. 2019

J. Cancer

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Background: Phosphodiesterase 4D (PDE4D) has recently been reported as an oncogene in various types of human cancers. However, the expression and significance of PDE4D in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated.Methods: Immunohistochemistry (IHC) was used to examine the expression of PDE4D in 104 clinicopathologically characterized PDAC cases. PDE4D expression in paired tumor tissues and adjacent noncancerous tissues were detected by western blotting and real time qRT-PCR. The correlation of PDE4D expression levels with clinicopathological features and prognosis in patients were analyzed by univariate and multivariate methods. Effect of PDE4D on pancreatic cancer cells was detected by cell migration and invasion assays.Results: We found that PDE4D was significantly up-regulated in PDAC tumor tissues compared to those paired adjacent noncancerous tissues at both protein and mRNA levels. High level of PDE4D was significantly associated with clinical stage (P = 0.004), T classification (P = 0.003), lymph node metastasis (P = 0.022) and liver metastasis (P = 0.038). Patients with higher levels of PDE4D had shorter overall survival time contrast with those with lower PDE4D expression (P = 0.002). Multivariate analysis indicated that PDE4D may be an independent prognostic factor for PDAC. PDE4D depletion significantly suppressed β-catenin and Snail expression as well as the migration and invasion abilities of pancreatic cancer cells.Conclusions: Our study reveals that PDE4D up-regulated in PDAC was closely associated with poor prognosis of PDAC patients and multiple aggressive clinicopathological characteristics. PDE4D could be a useful prognostic biomarker and therapeutic target for PDAC.

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Section: Discussionmentioning

confidence: 95%

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma

Liu¹,

Ma²,

Wang³

et al. 2019

J. Cancer

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“…To our knowledge, both PDE4D (phosphodiesterase 4D) and SERP2 (stress-associated endoplasmic reticulum protein family member 2) are associated with tumors [ 62 , 63 ]. Among them, PDE4D has been reported to act as a proliferation promoter in several different tumors [ 64 – 66 ], and mutations in SERP2 are associated with leukemia [ 67 ]. In our study, both the 2 loci were connected to Cer(d18:0/12:0), but further studies are needed to explore the specific relationship between the occurrence of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer

et al. 2021

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Background Metabolite genome-wide association studies (mGWAS) are key for understanding the genetic regulation of metabolites in complex diseases including cancers. Although mGWAS has revealed hundreds of metabolomics quantitative trait loci (mQTLs) in the general population, data relating to gastric cancer (GC) are still incomplete. Methods We identified mQTLs associated with GC by analyzing genome-wide and metabolome-wide datasets generated from 233 GC patients and 233 healthy controls. Results Twenty-two metabolites were statistically different between GC cases and healthy controls, and all of them were associated with the risk of gastric cancer. mGWAS analyses further revealed that 9 single nucleotide polymorphisms (SNPs) were significantly associated with 3 metabolites. Of these 9 SNPs, 6 loci were never reported in the previous mGWAS studies. Surprisingly, 4 of 9 SNPs were significantly enriched in genes involved in the T cell receptor signaling pathway. Conclusions Our study unveiled several novel GC metabolite and genetic biomarkers, which may be implicated in the prevention and diagnosis of gastric cancer.

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“…Numerous studies have demonstrated that PDE4D may function in cancer via different pathways, including the EGFR/phosphoinositide 3-kinase/protein kinase B signalling pathway, MAPK pathway and Hedgehog pathway ( 66 – 68 ). However, further exploration is required to clarify the potential molecular mechanisms of PDE4D in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of the predicted targets of miR-642b-3p associated with the long non-coding RNA HOXA11-AS in NSCLC cells

et al. 2018

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Long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) has been previously reported to be involved in the tumorigenesis and progression of ovarian cancer and glioma. However, the function of HOXA11-AS in lung cancer remains unclear. Following the knockdown of HOXA11-AS in A549 cells, a microarray analysis was performed in order to detect the differences in microRNA (miRNA/miR) profiles. Subsequently, miR-642b-3p was selected for further analysis. Four miRNA target prediction algorithms were used to identify potential target genes of miR-642b-3p. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes, protein-protein interactions (PPIs) and network analysis, were performed to investigate the potential functions, pathways and networks of the target genes. Furthermore, the differential expression of miR-642b-3p and its target genes between normal lung and non-small cell lung cancer (NSCLC) tissues was verified using The Cancer Genome Atlas (TCGA) database. Six target genes [zinc finger protein 350, heterogeneous nuclear ribonucleoprotein U, high mobility group box 1, phosphodiesterase 4D (PDE4D), synaptotagmin binding cytoplasmic RNA interacting protein and basic helix-loop-helix family member B9] of miR-642b-3p were predicted using all 4 algorithms. It was revealed that miR-642b-3p was overexpressed in adenocarcinoma and squamous cell carcinoma tissues compared with non-cancerous lung tissues based on the TCGA database. From the 6 target genes, PDE4D was downregulated in lung adenocarcinoma and squamous cell carcinoma tissues, and a weak negative correlation between HOXA11-AS and PDE4D was identified. The area under the curve of PDE4D was 0.905 [95% confidence interval (CI), 0.879–0.931] for patients with lung adenocarcinoma and 0.665 (95% CI, 0.606–0.725) for patients with squamous cell carcinoma. Additionally, GO analysis of the target genes revealed that miR-642b-3p was specifically involved in complex cellular pathways. The target gene RAN binding protein 2 possessed the highest degree of interactions in the PPI network (degree=40). It was hypothesized that HOXA11-AS may have a function in NSCLC by regulating the expression of miR-642b-3p and PDE4D, which laid the foundation for the further elucidation of the potential molecular mechanisms of NSCLC.

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Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway

Cited by 10 publications

References 23 publications

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma

mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer

A comprehensive analysis of the predicted targets of miR-642b-3p associated with the long non-coding RNA HOXA11-AS in NSCLC cells

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