Notes

β-actin primarily based chromatin redesigning mediates compartment stage changes in 3 dimensional genome structure.
VCL can affect EMT and tumor immunity by regulating EPCAM gene expression. The role and mechanism of action of vinculin have been controversial, but this molecule may downregulate EpCAM (epithelial cellular adhesion molecule) and its own role in gastric cancer through DNA methylation, causing NK cells to enrich into tumor cells and kill tumor cells. At the same time, it promotes the occurrence of EMT, which in turn causes tumor metastasis and thus poorer prognosis.Patients with heart failure are at increased risk for ischemic stroke. We aim to develop a more accurate stroke risk prediction tools identify high-risk patients with heart failure with reduced ejection fraction (HFrEF). Patient data were extracted retrospectively from the electronic medical database between January 2009 and February 2019. LY3295668 cell line Univariate and multivariate Cox regression analysis were performed to identify independent predictors, which were utilized to construct a nomogram for predicting ischemic stroke. AUROC analysis was used to compare the prognostic value between the new risk score and CHADS2/CHA2DS2-VASc scores. In 6087 patients with HFrEF, the risk of first-ever ischemic stroke was 5.8% events/pts-years (n=468) during 8007.2 person-years follow-up. A nomogram constructed by integrating 6 variables, including age, atrial fibrillation (AF), deep vein thrombosis (DVT), d-dimer, anticoagulant use and spontaneous echocardiographic contrast (SEC)/left ventricular thrombus (LVT), exhibited a greater area under the curve of 0.727, 0.728 and 0.714 than that by CHADS2 score (0.515, 0.522 and 0.540), and by CHA2DS2-VASc score (0.547, 0.553 and 0.562) for predicting first-ever ischemic stroke at hospitalization, 30-day and 6-month follow-up (all p less then 0.001). This novel stroke risk score performed better than existing CHADS2/ CHA2DS2-VASc scores and showed improvement in predicting first-ever ischemic stroke in HFrEF patients.In this study, we investigated the effect of a short deletion in the DNA-binding domain of STAT3 (STAT3del) on the transcriptional activation of STAT3 target genes and its relationship with colon carcinogenesis. We used the CRISPR-CAS9 gene editing system to delete a short sequence encoding amino acids 400-411 in the DNA-binding domain (amino acid sequence 317-567) from STAT3 gene in SW480, SW620 and HCT116 colon cancer cells. ChIP sequencing analysis showed that STAT3del occupancy was significantly reduced in 1029 genes and significantly increased in 475 genes compared to wild-type STAT3. The mutation altered the DNA motifs recognized by STAT3del as compared to the wild-type STAT3. We observed a strong correlation between expression of the STAT3 target genes and the loss or gain of STAT3del binding to their promoters. CCK-8, wound healing, and TUNEL assays showed reduced proliferation, migration, and survival of SW480, SW620 and HCT-116 cells expressing STAT3del as compared to the corresponding controls. These findings demonstrate that a short deletion in the DNA-binding domain of STAT3 alters its genome-wide DNA-binding and transcriptional profile of STAT3-target proteins, and suppresses the growth, progression and survival of colon cancer cells.
Lung cancer is the first fatality rate of cancer-related death worldwide. This study aimed to evaluate the solute carrier family 39 (SLC39A) genes as biological markers associated with the prognosis of lung adenocarcinoma (LUAD).

MRNA expression of SLC39A genes in non-small cell lung cancer (NSCLC) was analyzed using UCSC database. We investigated the overall survival (OS) of SLC39A genes in patients with NSCLC as the only prognostic indicator using the Kaplan-Meier plotter. CERES score obtained from the Project Achilles was used to perform the survival analysis. Crystal violet-glutaraldehyde solution staining and CCK-8 assay were used to determine colony formation and cell viability, respectively.

For patients with lung squamous cell carcinoma, only high expression of SLC39A3, SLC39A4 and SLC39A7 have significant affections to the prognosis. But for patients with LUAD, 11 out of 14 SLC39A genes were significantly associated with prognostic values. Additional analysis indicated that SLC39A7 played an essential role for cell survival of LUAD. Furthermore, SLC39A7 high expression in LUAD was associated with current smoking.

Our findings indicated that SLC39A groups were significantly associated with prognosis of LUAD. The SLC39A7 gene was significantly linked with survival and growth of LUAD cells.
Our findings indicated that SLC39A groups were significantly associated with prognosis of LUAD. The SLC39A7 gene was significantly linked with survival and growth of LUAD cells.It is important to identify novel biomarkers to improve hepatocellular carcinoma (HCC) diagnosis and treatment. Herein, we reported the role of karyopherin α4 (KPNA4) in HCC patients through public data mining and examined the results using clinical samples in our center. Our results revealed that KPNA4 expression level was positively correlated with the infiltration of CD8+ T cells, B cells, dendritic cells, CD4+ T cells, neutrophils and macrophages. In addition, KPNA4 expression was significantly associated with T cell exhaustion. KPNA4 mRNA and protein expression levels were significantly higher in cancerous tissue than in normal tissue. Besides, the increased expression of KPNA4 indicated poor overall survival. Univariate and multivariate Cox regression analyses showed KPNA4 could be viewed as an independent risk factor for HCC patients. Moreover, our experimental results were consistent with those obtained from bioinformatic results. These findings revealed KPNA4 may serve as a novel prognostic biomarker and a potential therapeutic target for HCC.In this study, we investigated the role of lncRNA MIR205HG in melanomagenesis. Quantitative real-time PCR (qRT-PCR) analysis showed that MIR205HG levels were significantly upregulated in melanoma cell lines compared to normal human melanocytes. Similarly, MIR205HG levels were significantly higher melanoma tissues than adjacent normal skin tissues (n=30). CCK-8 and flow cytometry assays showed that MIR205HG knockdown significantly decreased the viability of melanoma cells. Dual luciferase reporter and RNA pull-down assays confirmed that MIR205HG directly binds to microRNA (miR)-299-3p. Targetscan analysis and dual luciferase reporter assays showed that miR-299-3p directly binds to the 3'UTR of VEGFA mRNA. Wound healing and transwell invasion assays showed that MIR205HG knockdown decreased in vitro migration and invasiveness of melanoma cells, and these effects were reversed by treatment with miR-299-3p inhibitor. MIR205HG-silenced melanoma cells showed increased miR-299-3p expression and lower levels of both VEGFA mRNA and protein. Tumor volumes were significantly smaller in nude mice xenografted with MIR205HG knockdown melanoma cells than the controls. These results demonstrate that MIR205HG supports melanoma growth via the miR-299-3p/VEGFA axis. This makes MIR205HG a potential therapeutic target for the treatment of melanoma.
Inflammatory bowel disease (IBD) is a chronic idiopathic gastrointestinal disease. Increasing evidence suggests that microRNAs (miRNAs) may participate in the pathophysiology of IBD.

A miRCURY™ LNA Array and
hybridization were employed to screen for differentially expressed miRNAs (DEMs) in fecal specimens from 41 IBD patients (22 ulcerative colitis (UC), 19 Crohn's disease (CD)) and 23 healthy controls (HC). RT-qPCR was performed to confirm the findings. The DEMs target genes and corresponding biological functions were predicted by bioinformatics analysis.

Compared with HC, miR-16-5p in the feces was up-regulated both in UC and CD patients (p < 0.01), while miR-21-5p was up-regulated only in UC patients (p < 0.01). TargetScan 7.2, miRWalk, and miRDB were used to predict 216 public target genes of miR-16-5p and miR-21-5p, and six hub genes (PIK3R1, GRB2, SUZ12, NTRK2, Smurf2, and WWP1) were analyzed using the STRING database and Cytoscape. All the hub genes promote the occurrence and development of IBD-related colorectal cancer.

The elevated levels of miR-16-5p and miR-21-5p in feces of IBD patients have to guide significance for the noninvasive clinical diagnosis of IBD and have a warning effect on the occurrence of IBD-related colorectal cancer.
The elevated levels of miR-16-5p and miR-21-5p in feces of IBD patients have to guide significance for the noninvasive clinical diagnosis of IBD and have a warning effect on the occurrence of IBD-related colorectal cancer.This study aimed to investigate the therapeutic mechanism of Huankuile suspension (HKL), a typical traditional Chinese medicine, on ulcerative colitis (UC) in a rat model. UC model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. Then, the rats were randomly divided into three groups water treated group, HKL treated group and 5- amino salicylic acid (5-ASA) treated group. After 7 days treatment, the histological score in the HKL treated group was comparable with those in the control group. qRT-PCR and western blot demonstrated that HKL could significantly decreased pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, while having less effect on anti-inflammatory cytokines, including IL-4 and IL-10. Transcriptomic analysis identified 670 differentially expressed genes (DEGs) between HKL treated UC rats and water treated UC rats. These DEGs were mostly related with immune response. Besides, metabonomic profile revealed 136 differential metabolites which were significantly enriched in "pyrimidine metabolism", "glutathione metabolism", "purine metabolism" and "citrate cycle". Finally, integrated analysis revealed that metabonomic pathways including "steroid hormone biosynthesis", "pyrimidine metabolism", "purine metabolism", and "glutathione metabolism" were altered by HKL at both transcriptomic and metabonomic levels. HKL could inhibit inflammation and regulate bile metabolism, pyrimidine metabolism, purine metabolism, glutathione metabolism and citrate cycle.Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.
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