scholarly journals A distinct transcriptional profile in response to endothelial monocyte activating polypeptide II is partially mediated by JAK-STAT3 in murine macrophages

2019 ◽  
Vol 317 (3) ◽  
pp. C449-C456 ◽  
Author(s):  
Daniel D. Lee ◽  
Alexandra Hochstetler ◽  
Christina Murphy ◽  
Chinn-Woan Lowe ◽  
Margaret A. Schwarz
Keyword(s):  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Peritoneal Macrophages ◽  
Functional Genes ◽  
Transcription Profile ◽  
Signal Transducer ◽  
Inflammatory Gene Expression ◽  
Secreted Factors ◽  
Emap Ii ◽  
Transcription 3

Macrophages are important responders to environmental changes such as secreted factors. Among the secreted factors in injured tissues, the highly conserved endothelial monocyte activating polypeptide II (EMAP II) has been characterized to limit vessel formation, to be locally expressed near sites of injury labeling it a “find-me” signal, and to recruit macrophages and neutrophils. The molecular mechanisms mediated by EMAP II within macrophages once they are recruited are unknown. In this study, using a model of partially activated, recruited thioglycollate-elicited peritoneal macrophages, a transient, transcription profile of key functional genes in macrophages exposed to EMAP II was characterized. We found that EMAP II-mediated changes were elicited mainly through signal transducer and activator of transcription 3 (STAT3) as evidenced by increased Y705 phosphorylation and changes in activity and upstream of it, Janus associated kinase (JAK)1/2 upstream. Both inhibition of JAK1/2 and knockdown of Stat3 abrogated a subset of genes that are upregulated by EMAP II. Our results identify a rapid EMAP II-mediated STAT3 activation that coincides with altered pro- and anti-inflammatory gene expression in macrophages.

scholarly journals GH-Releasing Hormone Induces Cardioprotection in Isolated Male Rat Heart via Activation of RISK and SAFE Pathways

Endocrinology ◽  
2013 ◽  
Vol 154 (4) ◽  
pp. 1624-1635 ◽  
Author(s):  
Claudia Penna ◽  
Fabio Settanni ◽  
Francesca Tullio ◽  
Letizia Trovato ◽  
Pasquale Pagliaro ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Male Rat ◽  
Signal Transducer ◽  
Rat Hearts ◽  
Phosphoinositide 3 Kinase ◽  
Amp Activated Protein Kinase ◽  
Transcription 3 ◽  
Isolated Rat

Abstract GHRH stimulates GH synthesis and release from the pituitary and exerts direct effects in extrapituitary tissues. We have previously shown that pretreatment with GHRH reduces cardiomyocyte apoptosis and improves heart function in isolated rat hearts subjected to ischemia/reperfusion (I/R). Here, we determined whether GHRH given at reperfusion reduces myocardial reperfusion injury and investigated the molecular mechanisms involved in GHRH effects. Isolated rat hearts subjected to I/R were treated at the onset of reperfusion with: 1) GHRH; 2) GHRH+GHRH antagonist JV-1-36; 3) GHRH+mitochondrial ATP-dependent potassium channel inhibitor 5-hydroxydecanoate; 4) GHRH+mitochondrial permeability transition pore opener atractyloside; 5) GHRH+ phosphoinositide 3-kinase/Akt inhibitor Wortmannin (WM); and 6) GHRH+signal transducer and activator of transcription-3 inhibitor tyrphostin-AG490 (AG490). GHRH reduced infarct size at the end of reperfusion and reverted contractility dysfunction in I/R hearts. These effects were inhibited by either JV-1-36, 5-hydroxydecanoate, atractylosid, WM, or AG490. Western blot analysis on left ventricles showed GHRH-induced phosphorylation of either the reperfusion injury salvage kinases (RISK), phosphoinositide 3-kinase/Akt, ERK1/2, and glycogen synthase kinase-3β or signal transducer and activator of transcription-3, as part of the survivor activating factor enhancement (SAFE) pathway. GHRH-induced activation of RISK and SAFE pathways was blocked by JV-1-36, WM, and AG490. Furthermore, GHRH increased the phosphorylation of endothelial nitric oxide synthase and AMP-activated protein kinase and preserved postischemic nicotinamide adenine dinucleotide (NAD+) levels. These results suggest that GHRH protects the heart from I/R injury through receptor-mediated mechanisms, leading to activation of RISK and SAFE pathways, which converge on mitochondria and possibly on AMP-activated protein kinase.

scholarly journals lncRNA RHPN1-AS1 Serves as a Sponge for miR-3133 Modulating the Cell Proliferation of Retinoblastoma through JAK2

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Zhao-Na Li ◽  
Ming-Xu Ge ◽  
Li-Jun Cao ◽  
Zhong-Fang Yuan
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Signal Transducer ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Proliferation Activity ◽  
Rna Immunoprecipitation ◽  
Related Proteins ◽  
Transcription 3

Purpose. To investigate the effects of lncRNA RHPN1-AS1 on retinoblastoma (RB) and further explore its underlying molecular mechanisms. Methods. The expression of RHPN1-AS1, miR-3133, (JAK2), and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR. CCK-8, EDU, and flow cytometry assays were conducted to assess the proliferation activity and apoptosis of RB cells. Double fluorescein and RNA immunoprecipitation assays were performed to detect the interaction between RHPN1-AS1 and miR-3133 or miR-3133 and JAK2. Western blotting was performed to detect the expression of apoptosis-related proteins. Results. In RB cells, RHPN1-AS1 was upregulated. Silencing RHPN1-AS1 inhibited the activity of RB cells and promoted apoptosis. The expressions of proapoptotic factors (Bax and p53) were increased, while antiapoptotic factors (Bcl-2 and Survivin) were suppressed in siRHPN1-AS1 groups. Furthermore, we predicted and verified that RHPN1-AS1 regulated RB progression by targeting miR-3133/JAK2. In addition, siRHPN1-AS1 also inhibited oncogene STAT3 protein expression. Conclusion. lncRNA RHPN1-AS1 served as a sponge for miR-3133 to counteract miR-3133-mediated JAK2/STAT3 suppression, indicating that the lncRNA RHPN1-AS1 may be a potential therapeutic target for the treatment of RB.

scholarly journals Isolinderalactone Induces Cell Death via Mitochondrial Superoxide- and STAT3-Mediated Pathways in Human Ovarian Cancer Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7530
Author(s):  
Shakya Rajina ◽  
Woo Jean Kim ◽  
Jung-Hyun Shim ◽  
Kyung-Soo Chun ◽  
Sang Hoon Joo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Signal Transducer ◽  
Antitumor Activities ◽  
Mitochondrial Superoxide ◽  
Dependent Cell ◽  
Transcription 3 ◽  
Cell Proportion

The mortality rate of ovarian cancer (OC) worldwide increases with age. OC is an often fatal cancer with a curative rate of only 20–30%, as symptoms often appear after disease progression. Studies have reported that isolinderalactone (ILL), a furanosesquiterpene derivative extracted from the dried root of Lindera aggregata, can inhibit several cancer cell lines’ growth. However, the molecular mechanisms underlying ILL activities in human OC cells remain unexplored. This study investigated the antitumor activities of ILL in human OC cells by inducing mitochondrial superoxide (mtSO) and JAK-signal transducer and activator of transcription 3 (STAT3)-dependent cell death. ILL caused cell death in SKOV-3 and OVCAR-3 cells and increased the cell proportion in the subG1 phase. Additionally, ILL significantly induced mtSO production and reduced ROS production. Moreover, ILL downregulated mitochondrial membrane potential and the expression levels of anti-apoptotic Bcl-2 family proteins and superoxide dismutase (SOD)2. Results showed that ILL decreased phosphorylation of serine 727 and tyrosine 705 of STAT3 and expression of survivin, a STAT3-regulated gene. Furthermore, ILL-induced cell death was reversed by pretreatment of Mito-TEMPO, a mitochondria-specific antioxidant. These results suggest that ILL induces cell death by upregulation of mtSO, downregulation of mitochondrial SOD2, and inactivation of the STAT3-mediated pathway.

scholarly journals miR-6743-5p, as a direct upstream regulator of GRIM-19, enhances proliferation and suppresses apoptosis in glioma cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Fang Cao ◽  
Qiang Zhang ◽  
Wei Chen ◽  
Feng Zheng ◽  
Qishan Ran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Glioma Cells ◽  
Significant Inhibition ◽  
Signal Transducer ◽  
Upstream Regulator ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
And Migration ◽  
Transcription 3

Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been recognized as a tumor suppressor protein, which regulates cell growth, apoptosis, and migration by signal transducer and activator of transcription 3 (STAT3) signaling pathway and non-STAT3 pathway in glioma cells. Here, we investigated the molecular mechanisms that regulated GRIM-19 expression in glioma cells. By the TargetScan algorithm, four miRNAs, hsa-miR-17-3p, hsa-miR-423-5p, hsa-miR-3184-5p, and hsa-miR-6743-5p, were identified with the potential to bind with 3′-UTR of GRIM-19. Further miRNA inhibitor transfection and luciferase assays revealed that miR-6743-5p was able to directly target the 3′-UTR of GRIM-19. Additionally, miR-6743-5p expression was inversely related with GRIM-19 expression in glioma specimens and cell lines. Moreover, the inhibition of miR-6743-5p caused a significant inhibition of cell proliferation and a marked promotion of cell apoptosis in glioma cells, and this phenotype was rescued by GRIM-19 knockdown. Finally, the inhibition of miR-6743-5p expression suppressed the phosphorylation of STAT3, and the mRNA expression of CyclinD1 and Bcl-2, two target genes of STAT3, while miR-6743-5p mimic had the inversed effects. Treatment with STAT3 inhibitor AG490 partially rescued the proliferation-promoting and anti-apoptosis effects of miR-6743-5p overexpression or GRIM-19 knockdown. Collectively, miR-6743-5p may act as an oncomiRNA in glioma by targetting GRIM-19 and STAT3.

MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3

2020 ◽  
pp. 1-9
Author(s):  
Huiping Tan ◽  
Chunlin Wu ◽  
Bo Huang ◽  
Lei Jin ◽  
Xiangbing Jiang
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Biological Activities ◽  
Signal Transducer ◽  
Cell Proliferation And Migration ◽  
Induce Cell Apoptosis ◽  
And Migration ◽  
Transcription 3 ◽  
Proliferation And Migration

As a result of metastasis and high recurrence, ovarian carcinoma (OC) is one of the most frequent gynecological carcinomas affecting women up to now. In spite of advances in OC treatments, the molecular mechanisms underlying OC progression are still needed to be deeply understood. MicroRNAs (miRNAs) with aberrant expressions are widely known to regulate target genes so as to mediate diverse biological activities of tumor cells. In the present study, we inspected the expression profile and latent mechanism of miR-3666 in OC. First of all, our research revealed the down-regulated miR-3666 in OC cells. Furthermore, miR-3666 up-regulation could repress cell proliferation and migration as well as induce cell apoptosis in OC. In addition, we unmasked that miR-3666 targeted STAT3 (signal transducer and activator of transcription 3) and further down-regulated STAT3 expression. Moreover, adenylate kinase 4 (AK4) was transcriptionally enhanced by STAT3, and then miR-3666 restrained AK4 expression by mediating STAT3. In the end, rescue experiments depicted that miR-3666 suppressed the development of OC via STAT3-mediated AK4. We uncovered that miR-3666 inhibited the tumorigenesis and even development of OC via suppressing STAT3/AK4 axis, offering a novel biomarker and therapeutic target for OC.

Hypoxia is a potent inducer of the iron masterswitch hepcidin via Signal Transducer and Activator of Transcription 3 (STAT3)

2017 ◽  
Author(s):  
I Silva ◽  
V Rausch ◽  
T Peccerella ◽  
G Millonig ◽  
HK Seitz ◽  
...  
Keyword(s):  
Signal Transducer ◽  
Potent Inducer ◽  
Transcription 3

Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Protein C ◽  
Biological Function ◽  
Prognostic Markers ◽  
Biological Effects ◽  
Signal Transducer ◽  
Gastric Cancer Cells ◽  
Transcription 3

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

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