Signal Transducer And Activator Of Transcription 3 Expression Research Articles

Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity.

This study’s goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences.

The expression and clinical significance of signal transducer and activator of transcription 3, tumor necrosis factor α induced protein 8-like 2, and runt-related transcription factor 1 in breast cancer patients.

This study explored the expression and clinical significance of signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor α induced protein 8-like 2 (TIPE2), and runt-related transcription factor 1 (RUNX1) in breast cancer tissue. From October 2014 to October 2017, 68 breast cancer patients (68 breast cancer tissue specimens) who underwent a radical mastectomy in our hospital were set as the observation group and the corresponding normal tissue 3 cm away from the cancer tissue was selected as the control group. The expression levels of STAT3, TIPE2, and RUNX1 in the two groups were compared via immunohistochemical staining. Multiple logistic regression was then used to analyze the related risk factors affecting the 2-year prognosis of breast cancer patients. The receiver operating characteristic (ROC) curve was then plotted and the area under the ROC curve was calculated. The predictive values of STAT3, TIPE2, and RUNX1, and the predictive value of the three transcription factors combined on the 2-year prognostic survival of breast cancer patients were determined. (I) In the observation group, the positive expression of STAT3 and the negative expression of TIPE2 and RUNX1 were significantly higher than those in the control group (P<0.05). (II) Of the 68 patients, 51 survived within 2 years and 17 patients died. Positive STAT3 expression, negative TIPE2 expression, negative RUNX1 expression, poor histological differentiation, TNM stage III-IV, and distant metastasis were all identified as factors that can affect the 2-year prognosis of breast cancer patients (P<0.05). (III) The ROC curve analysis examining the 2-year prognostic survival of breast cancer patients showed that the area under the curve achieved the largest value when the predictive values of STAT3, TIPE2, RUNX1 were combined. The levels of STAT3, TIPE2, and RUNX1 expression in breast cancer tissues were significantly different from that in adjacent normal tissues. This suggested that the combined detection of STAT3, TIPE2, and RUNX1 may improve the rate of early breast cancer diagnosis. Furthermore, STAT3, TIPE2, and RUNX1 may be useful in evaluating the prognosis of the patients with breast cancer.

MiR-495 regulates cell proliferation and apoptosis in H2O2 stimulated rat spinal cord neurons through targeting signal transducer and activator of transcription 3 (STAT3).

BackgroundMicroRNA-495 (miR-495) is a post-translational modulator that performs several functions, and it is involved in several disease states. On the other hand, the physiological functions of miR-495 in H2O2 stimulated mouse spinal cord neuronal dysfunction have not yet been fully understood.MethodsIn this study, we speculated that miR-495 may regulate the expression of STAT3 in the processes of neuronal proliferation and apoptosis following spinal cord injury (SCI). Cell viability was assessed with methyl thiazolyl tetrazolium (MTT) assay. Caspase-3 activity was assayed with ELISA. Cellular apoptotic changes were measured with TUNEL assay. Intracellular ROS production was determined by measuring uptake of dichlorodihydrofluorescein diacetate (DCFH-DA; PCR was used to assay the mRNA expression of STAT3 gene bearing predicted targeting positions for miR-495, while qRT-PCR was used to measure miR-495 mRNA.ResultsThe results demonstrated that treatment of SCNs with H2O2 led to a significant decrease in cell survival, while it enhanced apoptosis. The H2O2 treatment induced cell membrane dysfunction, and increased ROS levels and DNA damage. Interestingly, the expression of miR-495 was markedly suppressed when SCNs were exposed to H2O2. However, miR-495 overexpression reversed H2O2-induced cytotoxicity and apoptosis in SCNs. Moreover, H2O2 exposure elevated protein and mRNA concentrations of STAT3 in SCNs. Bioinformatics analysis showed likely binding domains of miR-495 in the 3'-untranslated regions of STAT3 in SCNs. MiR-495 loss-of-function and gain-of-function significantly up-regulated and down-regulated both STAT3 mRNA and protein expressions, respectively, in SCNs.ConclusionsmiR-495 overexpression inhibited H2O2-induced SCN dysfunction. This mechanism was mediated through the down-regulation of STAT3 expression.

SMURF1-mediated ubiquitylation of SHP-1 promotes cell proliferation and invasion of endometrial stromal cells in endometriosis.

BackgroundEndometriosis is a widespread benign gynecological disorder. The signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in the pathogenesis of endometriosis through regulating proliferation and invasion of endometrial stromal cells. Furthermore, the protein tyrosine phosphatase (PTP), SH2 domain-containing phosphatase 1 (SHP-1), negatively regulates STAT3 activation. However, regulation of the SHP-1-STAT3 pathway in the pathogenesis of endometriosis remains unclear.MethodsCell proliferation and invasion were assessed by Cell Counting Kit-8 (CCK-8) assay and Transwell analysis, respectively, to investigate the role and regulation of the SHP-1-STAT3 pathway in the proliferation and invasion of endometrial stromal cells. Expression of Smad ubiquitin regulatory factor 1 (SMURF1), SHP-1, matrix metalloproteinase 2 (MMP2), MMP9, STAT3, and phospho-STAT3 (p-STAT3) level in patients with endometriosis were measured by Western blotting and/or immunohistochemical staining. The interaction between SMURF1 and SHP-1 was investigated by co-immunoprecipitation and ubiquitylation analysis.ResultsThe present study demonstrated that downregulation of SHP-1 expression in patients with endometriosis was negatively correlated with SMURF1 expression. SMURF1, an E3 ubiquitin ligase, activated the STAT3 pathway via ubiquitylation and degradation of SHP-1. Furthermore, SMURF1 promoted cell proliferation and invasion of endometrial stromal cells by activating STAT3 signaling and expression of its downstream targets, MMP2 and MMP9, whereas SHP-1 demonstrated an inverse effect. Additionally, SHP-1 inhibited SMURF1-mediated cell invasion and proliferation of endometrial stromal cells.ConclusionsOur findings indicate that SMURF1-mediated ubiquitylation of SHP-1 regulates endometrial stromal cell proliferation and invasion during endometriosis.

Biotherapeutic Effects of Salidroside on Gastric Carcinoma Cells

Salidroside is verified to have tumor inhibitory effects. Nevertheless, the mechanisms are not clarified. The research aims to explore the tumor inhibitory mechanisms of salidroside on gastric carcinoma. The tumor inhibitory effects were examined by the cell viability assay. Flow cytometric analysis was adopted to estimate the cancer cells apoptosis. The expressions of differentiated embryo-chondrocyte expressed gene 1 (DEC1), hypoxia-inducible factor-1α (HIF-1α) and signal transducer and activator of transcription 3 (STAT3) in carcinoma cells were measured by immunohistochemistry assay. Salidroside displayed definite cytotoxicity effects on gastric carcinoma cells in a dose and time dependent manner. Apoptotic percent in carcinoma cells treated with salidroside were significantly increased (P < 0.05). The migrations of cancer cells were suppressed with the increasing doses of salidroside. The expressions of HIF-1α, DEC1 and STAT3 in cancer cells with salidroside treatment were down-regulated. The findings suggested that salidroside suppressed the growth of gastric cancer cells by eliciting the cancer cells apoptosis and lowing the expressions of HIF-1α, DEC1 and STAT3 signal molecules.

MiR-467b alleviates lipopolysaccharide-induced inflammation through targeting STAT1 in chondrogenic ATDC5 cells.

Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide. Chondrocytes are activated in OA patients, accompanied by excessive chondrogenic proliferation and production of inflammatory cytokines. MiR-467b is implicated in the regulation of artherosclerosis and pro-inflammatory cytokine secretion. However, the precise role of miR-467b in OA remains unclear. In the present study, we induced inflammation in chondrogenic ATDC5 cells using lipopolysaccharide (LPS). LPS treatment significantly elevated the production of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α (TNF-α) in ATDC5 cells, accompanied by decreased miR-467 level. Then, we over-expressed miR-467b using its specific mimics in ATDC5 cells, and LPS-induced inflammation was significantly inhibited as evidenced by decreased IL-6, IL-1β and TNF-α levels. MiR-467b agomir also alleviated inflammation in rat knee osteoarthritis (KOA) model. In addition, we validated that signal transducer and activator of transcription 1 (STAT1) was a downstream target of miR-467b. LPS treatment significantly increased the STAT1 expression while miR-467b mimic transfection partially reversed this effect. Moreover, STAT1 knockout reversed the increased contents of IL-6, IL-1β and TNF-α. Furthermore, miR-467b over-expression significantly decreased the production of IL-6, IL-1β and TNF-α induced by LPS treatment, which was partially reversed by further STAT1 over-expression. In summary, our findings demonstrated that miR-467b alleviated LPS-induced inflammation through targeting STAT1, and this miR-467b/STAT1 regulation axis may provide a new therapeutic target for OA clinical management.

Characterization and clinical significance of the CADM1/HER2/STAT3 axis in serous ovarian tumors.

The subtypes of serous ovarian tumors (SOTs), including benign serous cystadenoma, serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSC), and high-grade serous ovarian carcinoma (HGSC), remain poorly understood. Herein, we aimed to characterize the cell adhesion molecule 1 (CADM1)/signal transducer and activator of transcription 3 (STAT3)/human epidermal growth factor receptor 2 (HER2) axis and identify its clinical significance in patients with serous cystadenoma, SBT, LGSC, and HGSC.The immunohistochemical expression of CADM1, HER2, and STAT3 was assessed in 180 SOT specimens, and its association with clinical data was determined.High levels of CADM1 expression were detected in 100% of serous cystadenomas and 83.33% of SBTs, while a loss of CADM1 expression was observed in 44% of LGSCs and 72.5% of HGSCs. Relative to the levels in benign cystadenomas and SBTs, higher levels of HER2 and STAT3 expression were observed in LGSCs and aggressive HGSCs. Furthermore, the expression profile of the CADM1/HER2/STAT3 axis was significantly associated with histologic type, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis in patients with SOT.Our study identified the changes in the CADM1/HER2/STAT3 axis that were closely associated with the clinical behavior of SOTs. These molecular data may provide new insights into SOT carcinogenesis and aid in the diagnosis and treatment of patients with SOT.

Quercetin Efficiently Alleviates TNF-α-Stimulated Injury by Signal Transducer and Activator of Transcription 1 and Mitogen-Activated Protein Kinase Pathway in H9c2 Cells: A Protective Role of Quercetin in Myocarditis.

This study aimed to evaluate the protective effect of quercetin and its in-depth mechanism in TNF-α-stimulated cardiomyocytes. The differential expression of TNF-alpha (TNF-α) and signal transducer and activator of transcription 1 (STAT1) was analyzed based on the GEO database. H9c2 cells were stimulated with TNF-α to simulate myocarditis. Cell counting kit-8 assay and flow cytometry assay were performed to detect the cell viability and apoptosis. ELISA was used to measure the levels of proinflammatory cytokines (IL-6 and IL-17A) and anti-inflammatory cytokine (IL-10). STAT1 expression was downregulated by transfection with si-STAT1, and its expression was detected using quantitative real-time polymerase chain reaction and Western blot. Western blot was also performed to assess the expression of the mitogen-activated protein kinase (MAPK) pathway-related factors. In this article, TNF-α was highly expressed in patients with myocarditis, and TNF-α (20 μg/mL) declined the viability of H9c2 cells. Quercetin pretreatment partially alleviated the decrease of cell viability, the increase of apoptosis, and the release of inflammatory cytokines (IL-10, IL-6, and IL-17A) induced by TNF-α. In addition, TNF-α increased STAT1 expression, but quercetin prevented the TNF-α-increased STAT1 level. Remarkably, knockdown of STAT1 enhanced the protective effect of quercetin on TNF-α-injured H9c2 cells. Moreover, quercetin restrained the TNF-α-induced activation of the MAPK pathway. Also, the inhibitory effect of quercetin on the pathway was aggravated by STAT1 lacking. In summing, quercetin plays a protective role in TNF-α-stimulated H9c2 cell injury, which may be related to the regulation of STAT1 and MAPK pathway.

The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression

BackgroundOsteosarcoma is one of the most prevalent primary bone tumours in adolescents. Accumulating evidence shows that aberrant expression of the long non-coding RNA (lncRNA) NEAT1 and microRNA-483 (miR-483) contribute to the epithelial-mesenchymal transition (EMT), invasion and metastasis of tumour cells. However, the potential regulatory effects of NEAT1 and miR-483 on the EMT of osteosarcoma remain elusive.MethodsThe expression of the NEAT1, miR-483, signal transducer and activator of transcription-1 (STAT1), STAT3, and EMT-associated markers was measured using qRT-PCR or western blotting. NEAT1 overexpression or knockdown was induced by lentivirus-mediated transfection. A luciferase reporter assay was employed to confirm the association between NEAT1/miR-483 and miR-483/STAT3. RNA immunoprecipitation (RIP) was also performed to verify the NEAT1 and miR-483 interaction. Wound healing and transwell assays were implemented to assess the migration and invasion of U2OS cells. Unilateral subcutaneous injection of U2OS into nude mice was performed to investigate tumour metastasis in vivo.ResultsThe expression of miR-483 was downregulated in both osteosarcoma cell lines and osteosarcoma tissues. The overexpression of miR-483 suppressed the migration, invasion, and expression of EMT-associated proteins in U2OS cells, while simultaneous overexpression of STAT3 partially relieved this suppression. Mechanistically, miR-483 specifically targeted the 3′ untranslated region (3′UTR) of STAT3 and repressed its expression. However, NEAT1 sponged miR-438, increased STAT3 expression, and repressed STAT1 expression, subsequently increasing the EMT of osteosarcoma cells. The knockdown of NEAT1 in transplanted U2OS cells impaired the liver and lung metastases of osteosarcoma in nude mice. Moreover, NEAT1 silencing inhibited the mesenchymal- epithelial transition (MET) of osteosarcoma at metastasis sites.ConclusionsThe lncRNA NEAT1/miR-483/STAT3 axis plays a crucial role in regulating the metastasis of osteosarcoma and potentially represents one appealing therapeutic target for osteosarcoma treatment in the future.

The effects of dexmedetomidine administered at various times on acute lung injury in rats.

To investigate the effects of dexmedetomidine (Dex) treatment administered at various times on acute lung injury (ALI). Thirty Wistar rats were randomly divided into five groups (n = 6/group). Lipopolysaccharide (LPS) was intraperitoneally injected into the rats in the LPS, Dex1, Dex2, and Dex3 groups to induce ALI, while the control group (C) was left untreated. Rats in the Dex1 group were intraperitoneally administered with 50 µg/kg Dex 30 minutes before modeling. Rats in the Dex2 group were injected with 25 µg/kg Dex 30 minutes before modeling and two hours after. Rats in the Dex3 group received 50 µg/kg Dex two hours after modeling. The animals in the C and LPS groups were given an equal volume of saline. The wet-to-dry (W/D) weight ratio of the rats' lungs was calculated, and pathological alterations in lung tissues were observed. The concentrations of inflammation-related factors and the expression of Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and matrix metallopeptidase 9 (MMP9) were measured. The W/D ratio, expression of inflammatory factors, and expression of JAK1, STAT3, and MMP9 were significantly increased in the ALI rats (p < 0.05) compared with the C group. The level of anti-inflammatory factors in the Dex-treated groups was also significantly increased compared with the LPS group (p < 0.05). The concentration of anti-inflammatory factors in the Dex2 group was significantly higher than that recorded in the Dex1 and Dex3 groups (p < 0.05). Dex treatment administered at different times protects rats against LPS-induced ALI to varying degrees. The protective effects of Dex were most robust when administered both before and after LPS stimulation.

Aloperine Inhibits Proliferation and Promotes Apoptosis in Colorectal Cancer Cells by Regulating the circNSUN2/miR-296-5p/STAT3 Pathway.

BackgroundAloperine can regulate miR-296-5p/Signal Transducer and Activator of Transcription 3 (STAT3) pathway to inhibit the malignant development of colorectal cancer (CRC), but the regulatory mechanism is unclear. This study explored the upstream mechanism of Aloperine in reducing CRC damage from the perspective of the circRNA-miRNA-mRNA regulatory network.MethodsAfter treatment with gradient concentrations of Aloperine (0.1 mmol/L, 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L and 1 mmol/L) for 24 hours, changes in CRC cell proliferation and apoptosis were detected by functional experiments. Data of the differential expression of miR-296-5p in CRC patients and healthy people were obtained from Starbase. The effects of Aloperine on 12 differentially expressed circRNAs were detected. The binding of miR-296-5p with NOP2/Sun RNA methyltransferase 2 (circNSUN2) and STAT3 was predicted by TargetScan and confirmed through dual-luciferase experiments. The expressions of circNSUN2, miR-296-5p and STAT3 as well as apoptosis-related genes in CRC cells were detected by qRT-PCR and Western blot as needed. Rescue experiments were conducted to test the regulatory effects of circNSUN2, miR-296-5p and STAT3 on CRC cells.ResultsAloperine at a concentration gradient inhibited proliferation and promoted apoptosis in CRC cells. The abnormally low expression of miR-296-5p in CRC could be upregulated by Aloperine. Among the differentially expressed circRNAs in CRC, only circNSUN2 not only targets miR-296-5p, but also can be regulated by Aloperine. The up-regulation of circNSUN2 offset the inhibitory effect of Aloperine on cancer cells. The rescue experiments finally confirmed the regulation of circNSUN2/miR-296-5p/STAT3 axis in CRC cells.ConclusionBy regulating the circNSUN2/miR-296-5p/STAT3 pathway, Aloperine prevents the malignant development of CRC cells.

Novel mutations in the signal transducer and activator of transcription 3 gene are associated with sheep body weight and fatness traits.

The signal transducer and activator of transcription 3 (STAT3) gene plays a crucial role in leptin-mediated energy metabolism, upon which the growth and development of animals depend. Nevertheless, no studies have reported the effects of STAT3 gene polymorphisms on body weight and fatness modulation in sheep. This study aimed to illustrate STAT3 mRNA expression across tissues and various developmental stages of sheep and to highlight the association of STAT3 gene polymorphisms with body weight and fat-related traits in sheep, in order to identify a genetic marker that may conceivably be of value for marker-assisted selection (MAS). This study revealed that STAT3 was differentially expressed across age and sex (p < 0.05), with higher expression in the ram liver. The abundant expression of STAT3 in the liver of male sheep and increased expression in the hypothalamus and longissimus dorsi muscle from birth to six months of age may indicate the vital role of the STAT3 gene in animal growth and development. Moreover, SNP association analysis also revealed that the novel SNPs of the STAT3 gene detected in this study showed a significant association with body weight and fatness traits (p < 0.05). In conclusion, the significant genetic effects of the STAT3 gene polymorphisms on sheep growth and development revealed that STAT3 could be a marker gene for the selection of growth-related traits in sheep.

HJC0416 Attenuates Fibrogenesis in Activated Hepatic Stellate Cells via STAT3 and NF-κB Pathways

BackgroundHepatic fibrosis is wound-healing response that is the result of hepatic stellate cell (HSC) activation and subsequent excess extracellular matrix deposition. HSCs can be activated by a variety of inflammatory stimuli as well as through the signal transducer and activator of transcription 3 (STAT3) pathway. HJC0416 is a novel, orally bioavailable small-molecule inhibitor of STAT3 that was developed by our team using a fragment-based drug design approach. Previously, our team has shown that HJC0416 has antifibrogenic effects in activated HSCs. Recently, increasing evidence suggests that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays an important role in the activation of HSCs. In the present study, we examined the role of NF-κB inhibition of HSC activation by HJC0416. MethodsLX-2 (human) and HSC-T6 (rat) cell lines were used. Expression levels of extracellular proteins, NF-κB and STAT3 expression and DNA binding, and inflammatory cytokine levels were determined using western blot, ELISA, and immunofluorescence assay. ResultsHJC0416 decreased cell viability in a dose-dependent manner in both cell lines and arrested the cell cycle at the S phase. Increased apoptosis was seen in LX-2 cells through Yo-Pro-1 and propidium iodide immunofluorescent stating. HJC0416 significantly decreased expression of fibronectin and collagen I as well as markedly decreased α-SMA and laminin. HJC0416 inhibited the STAT3 pathway by decreasing phosphorylation of STAT3, as well as signal transduction pathway activation. Notably, HJC0416 also inhibited the classic and alternative pathways of NF-κB activation. HJC0416 inhibited LPS-induced p65 nuclear translocation and DNA binding, as well as prevented phosphorylation and degradation of inhibitory protein IκBα. HJC0416 also prevented phosphorylation of serine residue 536 on p65. ConclusionsHJC0416, an inhibitor of STAT3, was found to have antifibrogenic properties in activated hepatic stellate cell lines. In addition, HJC0416 was found to inhibit the NF-κB pathway. Owing to this double effect, HJC0416 demonstrates promise for in vivo experimentation as an antifibrosis treatment.

IL‐6/STAT3‐mediated autophagy participates in the development of age‐related glomerulosclerosis

The standard of age-related glomerulosclerosis is unclear. Both signal transducer and activator of transcription 3 (STAT3) and autophagy are involved in age-related kidney disease. Therefore, we aimed to explore the standard, as well as the potential mechanism(s). A total of 44 patients who underwent radical nephrectomy were enrolled. Pearson analysis was performed to investigate the parameters with ages. The patients were divided into the young-and aged-kidney groups. Kidney morphological changes were evaluated by histology staining, senescence was evaluated by senescence-associated-β-galactosidase (SA-β-gal) staining, and autophagosome was measured by transmission electron microscopy. Moreover, Western blot and/or immunohistochemistry were accomplished to assess the expression of p16, STAT3, and glycoprotein130 (GP130) and autophagy-related proteins. Furthermore, human glomerular mesangial cells were administrated with tocilizumab (TCZ) and/or IL-6, and then the above indexes were tested again. Sclerotic glomerular density and glomerular sclerosis rate were significantly higher in individuals more than 40 years old, and they were strongly correlated with ages. Moreover, the expression of p16, STAT3, GP130, and p62 was significantly increased, while LC3II and autophagosome were statistically decreased in the aged-kidney. Glomeruli were hardly to stain with SA-β-gal. For the in vitro experiments, we observed that IL-6 significantly increased p16, STAT3, GP130, and p62, induced higher SA-β-gal staining, while downregulated LC3II and autophagosome. Furthermore, TCZ statistically reversed the effects of IL-6 on the above expression of proteins. Glomerular sclerosis rate might be one standard for natural renal aging, and IL-6/STAT3-mediated autophagy may participate in the development of age-related glomerulosclerosis.

Protective effects of Atractylenolide III on inflammation and oxidative stress in ovalbumin-induced asthma mice and its possible mechanisms.

Asthma is a complex disorder characterized by chronic inflammation of the airways. We aimed to investigate the role of Atractylenolide III (ATL III) in ovalbumin (OVA)-induced mouse asthma. Asthma was induced to BALB/c mice by sensitization with intraperitoneal injection of OVA, followed by treatment with ATL III. Pathological changes in lung tissue were examined by hematoxylin/ eosin and sirius red staining. The levels of inflammation- and oxidative stress-related factors in the bronchoalveolar lavage fluid (BALF) were monitored using kits. Additionally, the contents of inflammatory cells including macrophages, lymphocytes, eosinophils and neutrophils in BALF were counted. The expression of signal transducer and activator of transcription 3 (STAT3) was tested using Western blotting and immunohistochemistry assay. Results revealed that ATL III markedly attenuated OVA-induced pathological injury of lung tissues in mice. Furthermore, ATL III controlled the cytokines production and balanced the oxidative stress condition, which was exhibited by the reduced levels of inflammation- and oxidative stress-related factors. Moreover, mice in ATL III-treated groups presented less inflammatory cells in BALF and ATL III largely inhibited STAT3 expression in lung tissues. Taken together, ATL III alleviates inflammation, oxidative stress and is associated with changes in pulmonary functions in a mouse asthma model through inhibiting STAT3.

Long non-coding RNA LINC00511 regulates the expression of microRNA-625-5p and activates signal transducers and activators of transcription 3 (STAT3) to accelerate the progression of gastric cancer

ABSTRACT This study aimed to investigate the expression, biological function, and downstream mechanism of LINC00511 in gastric cancer (GC). In paired GC samples, LINC00511, miR-625-5p and STAT3 mRNA expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR); STAT3 protein expression was detected by immunohistochemical (IHC). The gain-of-function and loss-of-function models were established, and the proliferative and migrative ability of GC cells were measured by CCK-8 and transwell assays, respectively. The regulatory relationship between miR-625-5p and LINC00511 or STAT3 was examined by bioinformatics analysis, luciferase reporter gene assay, qRT-PCR, and western blot. We reported that LINC00511 and STAT3 expressions in GC tissues and cell lines were observably up-regulated, while miR-625-5p expression was inhibited. High expression of LINC00511 could facilitate the proliferation and promote the migration of GC cells. miR-625-5p was proved to be a downstream target of LINC00511, and LINC00511 could induce the expression of STAT3 by inhibiting the expression of miR-625-5p. Additionally, knockdown of LINC00511 suppressed the growth and lung metastases of CRC cells in nude mice. In conclusion, LINC00511 promotes the GC cell proliferation and migration via targeting the miR-625-5p/STAT3 axis, implying that LINC00511 can function as a target for GC therapy.

Does signal transducer and activator of transcription-3 have a role in lichen planus?

ObjectiveThe aim was to evaluate the role of signal transducer and activator of transcription 3 (STAT3) in lichen planus (LP).BackgroundLP is a chronic mucocutaneous T-cell-mediated inflammatory disease. STAT3 is responsible for signal transmission to the nucleus from many receptors and nonreceptor-associated kinases.Materials and methodsA prospective case–control study was conducted on 20 cases with LP and 20 age-matched, sex-matched, and localization-matched apparently healthy participants. All sections were immunohistochemically stained for STAT3.ResultsThere were significant differences between the studied groups regarding STAT3 positivity in both dermis and epidermis (P = 0.043 for both), as well as STAT3 intensity of expression in epidermis and dermis (P = 0.008 and 0.001, respectively). There were significant associations between moderate and strong STAT3 expression and generalized lesions, presence of precipitating factors, presence of dermal melanophages, and presence of moderate spongiosis (P = 0.01, 0.005, 0.05, and 0.04, respectively).ConclusionOverexpression of STAT3 in LP could play a role in pathogenesis and severity of LP. Anti-STAT3 target therapy might be suggested to ameliorate LP.

Inhibition of microRNA-874 ameliorates cardiomyocyte apoptosis and improves cardiac function in the peripartum cardiomyopathy of Gαq transgenic mice

It is widely reported that microRNAs (miRNAs, miRs) play critical roles in the occurrence and development of peripartum cardiomyopathy (PPCM). Here, we aimed to explore the biological role of miR-874 and its underlying mechanisms in PPCM. To this purpose, a mouse model of PPCM was established through cardiac-specific overexpression of Gαq. Transthoracic echocardiography and left ventricular catheterization were used to examine the cardiac functions and hemodynamics. Apoptosis of the cardiomyocytes was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The direct interaction between miR‐874 and signal transducer and activator of transcription 3 (STAT3) was confirmed by luciferase assay. The expression of apoptosis-related genes and proteins was evaluated by real-time quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The results demonstrated that miR-874 inhibition significantly increased the survival and cardiac functions of pregnant Gαq transgenic mice. In addition, miR-874 inhibitor ameliorated cardiomyocyte apoptosis, downregulated both mRNA and protein levels of Bax, while upregulated those of Bcl-2. Further, STAT3 was found to be a direct target of miR-874. In addition, miR-874 inhibition increased the expression of STAT3 and janus kinase 2. In summary, miR-874 inhibition could improve cardiac functions and suppress cardiomyocyte apoptosis by targeting STAT3 during PPCM in Gαq transgenic mice.

Enhancer of zeste homolog 2 participates in the process of atherosclerosis by modulating microRNA-139-5p methylation and signal transducer and activator of transcription 1 expression.

Atherosclerosis (AS) is the main cause of coronary heart disease, in which enhancer of zeste homolog 2 (EZH2) has been implied to participate in this process. Thus, this work proposed to explore the effect of EZH2 on AS from microRNA-139-5p (miR-139-5p)/signal transducer and activator of transcription 1 (STAT1) axis. EZH2, miR-139-5p, and STAT1 expression in arterial tissues of AS patients were detected. Human arterial smooth muscle cells (HASMCs) induced with oxidized low-density lipoprotein (ox-LDL) and the mice fed with high fat diet were treated with silenced EZH2 or upregulated miR-139-5p to explore their roles in proliferation and apoptosis of HASMCs, together with inflammation response and oxidative stress of mice. Chromatin immunoprecipitation experiment was applied to verify the regulatory effect of EZH2 on miR-139-5p through methylation of H3K27me3. The targeting relationship between miR-139-5p and STAT1 was verified by online website and luciferase activity assay. Reduced miR-139-5p and overexpressed EHZ2 and STAT1 were found in AS. Silenced EZH2 or elevated miR-139-5p decreased the production of cholesterol and inhibited inflammation reaction in serum of mice with AS. Silenced EZH2 or elevated miR-139-5p facilitated proliferation and restrained apoptosis of ox-LDL-treated HASMCs, and restrained oxidative stress and cell apoptosis in arterial tissues of AS mice. EZH2 regulated miR-139-5p through H3K27me3, and miR-139-5p targeted STAT1. miR-139-5p silencing antagonized the effects of EZH2 down-regulation on AS. This study manifests that down-regulated EZH2 or elevated miR-139-5p inhibits ox-LDL-induced HASMCs apoptosis, plaque formation, and inflammatory response in AS mice, which may be related to down-regulated STAT1.

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1

BackgroundAccumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice. MethodsA mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested. ResultsmiR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1. ConclusionFunctional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.