Role of STAT3 as a Negative Regulator in Mac2- Binding Protein Expression

Park, Yuk Pheel; Kim, Jong-Tae; Yang, Young; Lim, Jong‐Seok; Yoon, Do Young; Kim, Jong Wan; Lee, Hee Gu

doi:10.3343/kjlm.2008.28.3.230

Cited by 2 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To examine whether Stat3 was functionally active in S16 cells, we examined the expression of the STAT3 upregulated targets, MMP7 31 , Bcl-2 32 and downregulated target, Mac-2bp 33 in S16 and C9 cells. Upregulation of MMP7 and Bcl-2 while down-regulation of Mac-2BP mRNA was observed in S16 cells as compared to C9 cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

Yeh

Chang

Lin

et al. 2016

Sci Rep

View full text Add to dashboard Cite

While aberrant JAK/STAT signaling is crucial to the development of gastric cancer (GC), its effects on epigenetic alterations of its transcriptional targets remains unclear. In this study, by expression microarrays coupled with bioinformatic analyses, we identified a putative STAT3 target gene, NR4A3 that was downregulated in MKN28 GC daughter cells overexpressing a constitutively activated STAT3 mutant (S16), as compared to an empty vector control (C9). Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetically silenced by promoter DNA methylation in S16 and other GC cell lines including AGS cells, showing constitutive activation of STAT3. Subsequent experiments revealed that NR4A3 promoter binding by STAT3 might repress its transcription. Long-term depletion of STAT3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells. NR4A3 re-expression in GC cell lines sensitized the cells to cisplatin, and inhibited tumor growth in vitro and in vivo, in an animal model. Clinically, GC patients with high NR4A3 methylation, or lower NR4A3 protein expression, had significantly shorter overall survival. Intriguingly, STAT3 activation significantly associated only with NR4A3 methylation in low-stage patient samples. Taken together, aberrant JAK/STAT3 signaling epigenetically silences a potential tumor suppressor, NR4A3, in gastric cancer, plausibly representing a reliable biomarker for gastric cancer prognosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

Yeh

Chang

Lin

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Thus, myxinidin2 and myxinidin3 modulated inflammatory signaling via IL-6, IL-8, TNF-α, STAT3 [ 34 ], p38 [ 35 ], JNK, and NF-κB and enhanced wound-closure activity by inducing the migration of primary keratinocytes [ 36 ], which involves transactivation of EGFR [ 37 ]. STAT3 is a multifunctional protein upregulated in inflammation, and its downregulation leads to anti-inflammatory activity [ 38 ] and cell growth through stimulation of EGF [ 39 , 40 ]. Infected keratinocytes treated with myxinidin2 or myxinidin3 showed higher levels of STAT3 phosphorylation than uninfected cells.…”

Section: Discussionmentioning

confidence: 99%

Myxinidin2 and myxinidin3 suppress inflammatory responses through STAT3 and MAPKs to promote wound healing

Han

Cheong

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Skin wounds are continuously exposed to bacteria and can easily become infected. Infected wounds require antibiotic treatment, and infections caused by drug-resistant bacteria are an important public health problem. Antimicrobial peptides have broad-spectrum antibacterial activity, induce little or no drug resistance and may be suitable for treating skin infections caused by drug-resistant bacteria. We previously reported the design and function of myxinidin and myxinidin analogues. Here we showed that myxinidin2 and myxinidin3 exhibit antimicrobial and anti-biofilm activities against antibiotic-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa in high salt environments and in gelatin. Moreover, these peptides facilitated infected wound healing by decreasing inflammation through suppression of IL-6, IL-8, and TNF-α and regulation of downstream mediators such as STAT3, p38, JNK, and EGFR. In a mouse skin wound model infected with antibiotic-resistant bacteria, myxinidin2 and myxinidin3 eliminated the infection and enhanced wound healing. We therefore propose the use of these peptides for treating infected wounds and burns.

show abstract

Role of STAT3 as a Negative Regulator in Mac2- Binding Protein Expression

Cited by 2 publications

References 38 publications

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer

Myxinidin2 and myxinidin3 suppress inflammatory responses through STAT3 and MAPKs to promote wound healing

Contact Info

Product

Resources

About