Polymorphisms in<i>PRKCDBP</i>, a Transcriptional Target of TNF-α, Are Associated With Inflammatory Bowel Disease in Korean

Kim, Jung-Wook; Lee, Chang Kyun; Kim, Hyo Jong; Shim, Jae‐Jun; Jang, Jae Young; Dong, Seok Ho; Kim, Byung-Ho; Chang, Young Woon; Chi, Sung–Gil

doi:10.5217/ir.2015.13.3.242

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…We compared the PRKCDBP OE A549/DDP group and the PRKCDBP NC A549/DDP group by mRNA expression profiling, and it was found that TNF-α could regulate PRKCDBP. These results are consistent with some literature reports (17,20,21). TNF-α resulted in an increase of the PRKCDBP mRNA level, while TNF-α siRNA led to a decrease thereof (P<0.001).…”

Section: Discussionsupporting

confidence: 93%

Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α

Zhou

Chen

et al. 2020

Oncol Rep

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The aim of the present study was to explore the mechanism of protein kinase C delta binding protein (PRKCDBP) promoting cisplatin resistance in lung adenocarcinoma (LAD). The PRKCDBP expression level was herein detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We overexpressed PRKCDBP and tumor necrosis factor-α (TNF-α) in A549/DDP cell line, DNMT1 in A549 cells and siRNA TNF-α in A549 cells with lentivirus-mediated technique, and then, analyzed their biological diversification. The results showed a significantly lower expression level of PRKCDBP was lowly expressed in the A549/DDP cell line and LAD tissues than that in A549 cells and adjacent cancer tissues (P<0.05 and P<0.01), while the DNMT1 mRNA level was remarkably increased (P=0.000) and the promoter of PRKCDBP was hypermethylated in the A549/DDP cell line. Additionally, DNMT1 mRNA level in cisplatin-insensitive group was markedly higher than that in cisplatin-sensitive group (t=7.233, P<0.0001), while PRKCDBP mRNA level in cisplatin insensitive group was notably lower than that in cisplatin-sensitive group (t=8.784, P<0.0001). The results showed that PRKCDBP mRNA level was significantly elevated following treatment with 5 µM decitabine for 24 h (P<0.0001), while the DNMT1 mRNA level was notably reduced (P=0.000). When PRKCDBP was overexpressed, the DNMT1 mRNA level was markedly decreased (P=0.007), the rate of proliferation (P<0.05 or P<0.01), IC50 of cisplatin (P<0.001), G2/M phase and S phase cells were obviously reduced (P<0.001), while G0/G1 phase cells, apoptosis (P<0.001) distinctly increased, but migration ability did not significantly change. TNF-α overexpression resulted in an increase of PRKCDBP mRNA level (P<0.001), while TNF-α siRNA led to PRKCDBP mRNA level distinctly reduced (P<0.001). Overexpression of DNMT1 improved IC50 in A549 cells. Thus, findings of the present study ascertained the promoter of PRKCDBP was hypermethylated in A549/DDP cells. In conclusion, low expression of PRKCDBP promoted cisplatin resistance in LAD by DNMT1 and TNF-α.

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Section: Discussionsupporting

confidence: 93%

Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α

Zhou

Chen

et al. 2020

Oncol Rep

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“…CDX1 promoter methylation was highly consistent with NF-κB signal activation, but inversely associated with TNF-α expression in the carcinogen-induced stomach cancer development 43 . TNF-α-induced hypermethylation of PRKCDBP was associated with NF-κB activation in the tumor suppressive effect of PRKCDBP in colorectal cancer 47 . TNF-β stimulation causes cadherin and collagen 1/g1 methylation by DNMT activation in the EMT and metastasis in ovarian cancer 48 .…”

Section: Discussionmentioning

confidence: 95%

IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation

et al. 2018

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The low expression of tissue inhibitor of metalloproteinase 3 (TIMP-3) is important in inflammatory responses. Therefore, inhibition of TIMP-3 may promote tumor development. Our study showed that expression of TIMP-3 was elevated in lL-32γ mice lung tissues. In this study, we investigated whether IL-32γ mice inhibited lung tumor development through overexpression of TIMP-3 and its methylation. To explore the possible underlying mechanism, lung cancer cells were transfected with IL-32γ cDNA plasmid. A marked increase in TIMP-3 expression was caused by promoter methylation. Mechanistic studies indicated that TIMP-3 overexpression reduced NF-κB activity, which led to cell growth inhibition in IL-32γ transfected lung cancer cells. We also showed that IL-32γ inhibits expression of DNA (cytosine-5-)-methyltransferase 1 (DNMT1). Moreover, IL-32γ inhibits the binding of DNMT1 to TIMP-3 promoter, but this effect was reversed by the treatment of DNA methyltransferase inhibitor (5-Aza-CdR) and NF-κB inhibitor (PS1145), suggesting that a marked increase in TIMP-3 expression was caused by inhibition of promoter hypermethylation via decreased DNMT1 expression through the NF-κB pathway. In an in vivo carcinogen induced lung tumor model, tumor growth was inhibited in IL-32γ overexpressed mice with elevated TIMP-3 expression and hypomethylation accompanied with reduced NF-κB activity. Moreover, in the lung cancer patient tissue, the expression of IL-32 and TIMP-3 was dramatically decreased at a grade-dependent manner compared to normal lung tissue. In summary, IL-32γ may increase TIMP-3 expression via hypomethylation through inactivation of NF-κB activity, and thereby reduce lung tumor growth.

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“…A previous study found that CaMK1, a class of protein kinases, could regulate protein phosphorylation by binding to Ca (2+)/calmodulin, and the polymorphism in the calmodulin-dependent kinase isomer D (CaMK1D) gene was associated with the development of diabetes as well as improved insulin sensitivity and glycemic control in obese mouse model ( Fromont et al., 2020 ). The polymorphisms in the PRKCDBP gene can be used as a transcriptional target for TNF-α to cause intestinal inflammatory diseases ( Kim et al., 2015 ). In the current study, the interaction between the upregulation of CaMK1 and PRKCDBP genes and these microbes ( Mycoplasma_sp._CAG:472 , Clostridium_sp._CAG:793 , and Akkermansia glycaniphila ) in the cecum were also highly correlated in the correlation network, suggesting a key regulatory function of lipid metabolism and the immune response in the mucosal layer of the cecum.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet

Li,

Qi,

Wang

et al. 2024

Front. Cell. Infect. Microbiol.

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The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus_sp._CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila, Clostridium_sp._CAG:793, Mycoplasma_sp._CAG:776, Mycoplasma_sp._CAG:472, Clostridium_sp._CAG:609, Akkermansia_sp._KLE1605, Clostridium_sp._CAG:508, and Firmicutes_bacterium_CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1, IGFBP6, and IGFBP4 genes were highly correlated with Clostridium_sp._CAG:793, and Akkermansia_glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity.

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Polymorphisms inPRKCDBP, a Transcriptional Target of TNF-α, Are Associated With Inflammatory Bowel Disease in Korean

Cited by 4 publications

References 29 publications

Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α

Low expression of PRKCDBP promoted cisplatin resistance in lung adenocarcinoma by DNMT1 and TNF‑α

IL-32 gamma reduces lung tumor development through upregulation of TIMP-3 overexpression and hypomethylation

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet

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