Expression Of ESM1 Research Articles

Blood endocan as a biomarker for breast cancer recurrence.

Endocan was reported to affect breast cancer patients negatively and was able to be detected from patients' blood. This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

The role of ESM1 in the lipids metabolic reprogramming and angiogenesis of lung adenocarcinoma cells

BackgroundLung adenocarcinoma (LUAD) is one of the respiratory diseases with high mortality and incidence. As an important angiogenic factor, (Endothelial cell-specific molecule 1) ESM1 plays an important role in the occurrence and development of LUAD. However, the role and molecular mechanism of ESM1 on LUAD metabolic reprogramming and angiogenesis remain unclear. MethodsWe used multiple databases to analyze the prognostic significance and potential function of ESM1 in patients with LUAD. The expression of ESM1 in LUAD cells was down-regulated/overexpressed by RNA interference, and the effects of ESM1 on the proliferation, migration, lipid metabolism and angiogenesis of LUAD cells in vitro and in vivo were analyzed using MTT, EdU, wound healing, oil red O, tubule formation, xenograft tumor model and chicken embryo allantoic model. ResultsESM1 is closely associated with poor prognosis in LUAD patients. ESM1 promotes LUAD proliferation, migration, fatty acid synthesis and angiogenesis. It also accelerates the proliferation, migration, lipid synthesis and tubule formation of endothelial cells in the tumor microenvironment in the form of secreted protein. Mechanically, ESM1 can promote the activation of AKT signaling pathway and up-regulate the expression of SCD1 and FASN. ConclusionOur results suggest that ESM1 promotes the proliferation, migration, lipid reprogramming, and angiogenesis of LUAD cells by activating the AKT signaling pathway, suggesting that ESM1 may be a potential therapeutic target and prognostic marker in LUAD patients.

Oncogenic HPV-induced high expression of ESM1 predicts poor prognosis and regulates aerobic glycolysis in cervical cancer

The impact of endothelial cell-specific molecule 1 (ESM1) on the initiation and progression of diverse cancers has been extensively studied, yet its regulatory mechanisms in relation to cervical cancer remain insufficiently understood. Through bioinformatics analysis, we revealed that ESM1 was highly expressed in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and correlated with dismal clinicopathological features. The activation of ESM1 is facilitated by the presence of oncogenic HPV E6 and E7. HPV E6 and E7 enhance the expression of ESM1 by diminishing the levels of miR-205-5p, which specifically targets the 3' untranslated region of ESM1 mRNA. In addition, we demonstrated that ESM1 facilitates aerobic glycolysis of cervical cancer cells via the Akt/mTOR pathway. Suppression of ESM1 led to a reduction in the expression of HIF-1α and multiple glycolytic enzymes. Taken together, our findings provide insights into the mechanisms by which HPV infections regulate oncogenes, thereby contributing to cervical carcinogenesis.

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

BackgroundThe hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined.MethodsLiquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments.ResultsOur findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry.ConclusionOur findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.

Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a secreted proteoglycan, with notable expression in kidney, which attenuates inflammation and albuminuria. However, little is known about Esm1 expression in mature tissues in the presence or absence of diabetes. We utilized publicly available single-cell RNA sequencing data to characterize Esm1 expression in 27,786 renal endothelial cells (RECs) obtained from three mouse and four human databases. We validated our findings using bulk transcriptome data from 20 healthy subjects and 41 patients with DKD and using RNAscope. In both mice and humans, Esm1 is expressed in a subset of all REC types and represents a minority of glomerular RECs. In patients, Esm1(+) cells exhibit conserved enrichment for blood vessel development genes. With diabetes, these cells are fewer in number and shift expression toward chemotaxis pathways. Esm1 correlates with a majority of genes within these pathways, delineating a glomerular transcriptional polarization reflected by the magnitude of Esm1 deficiency. Diabetes correlates with lower Esm1 expression and with changes in the functional characterization of Esm1(+) cells. Thus, Esm1 appears to be a marker for glomerular transcriptional polarization in DKD.NEW & NOTEWORTHY Esm-1 is primarily expressed in glomerular endothelium in humans. Cells expressing Esm1 exhibit a high degree of conservation in the enrichment of genes related to blood vessel development. In the context of diabetes, these cells are reduced in number and show a significant transcriptional shift toward the chemotaxis pathway. In diabetes, there is a transcriptional polarization in the glomerulus that is reflected by the degree of Esm1 deficiency.

Novel specific anti-ESM1 antibodies overcome tumor bevacizumab resistance by suppressing angiogenesis and metastasis.

Suppressing tumors through anti-angiogenesis has been established as an effective clinical treatment strategy. Bevacizumab, a monoclonal antibody, is commonly used in various indications. However, two major challenges limit the long-term efficacy of bevacizumab: drug resistance and side effects. Bevacizumab resistance has been extensively studied at the molecular level, but no drug candidates have been developed for clinical use to overcome this resistance. In a previous study conducted by our team, a major finding was that high expression of ESM1 in bevacizumab-resistant tumors is associated with an unfavorable response to treatment. In particular, an increase in ESM1 expression contributes to heightened lung metastasis and microvascular density, which ultimately decreases the tumor's sensitivity to bevacizumab. In contrast, the silencing of ESM1 results in reduced angiogenesis and suppressed tumor growth in tumors resistant to bevacizumab. We put forward the hypothesis that targeting ESM1 could serve as a therapeutic strategy in overcoming bevacizumab resistance. In this study, a variety of anti-ESM1 antibodies with high affinity to human ESM1 were successfully prepared and characterized. Our in vivo study confirmed the establishment of a bevacizumab-resistant human colorectal cancer model and further demonstrated that the addition of anti-ESM1 monoclonal antibodies to bevacizumab treatment significantly improved tumor response while downregulating DLL4 and MMP9. In conclusion, our study suggests that anti-hESM1 monoclonal antibodies have the potential to alleviate or overcome bevacizumab resistance, thereby providing new strategies and drug candidates for clinical research in the treatment of bevacizumab-resistant colorectal cancer.

Identification of ESM1 as a Potential Biomarker Involving Drug Sensitivity and the Tumor Immune Microenvironment that Promotes Proliferation of Melanoma.

ESM1 may play a role in human cancers, but its role in melanoma remains unclear. This study investigated ESM1 expression in Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed it through immunohistochemistry (IHC) and Western blotting (WB). Using the ESM1 gene expression levels, we divided TCGA samples into high and low-expression groups and identified differentially expressed genes (DEGs) between them. We then performed GO and KEGG enrichment analyses on these DEGs and explored the immune landscape while identifying anti-tumor drugs. ESM1 was found to be highly expressed in metastatic melanoma compared to primary melanoma and normal tissues. This was associated with increased numbers of immune-related cells and genes, as well as the activation of tumor progression pathways such as Notch and Wnt. In the high ESM1 expression group, the number of multiple immune-related cells and the expression of immune-related genes correlated with the presentation of ESM1, as well as the agonism of pathways related to tumor progressions. Immunohistochemistry and WB demonstrated a significant increase in ESM1 expression in metastatic lesions. Multiple GEO datasets showed higher ESM1 mRNA expression in malignant melanoma than in other benign tumors. ESM1 knockdown in a mouse model reduced tumor volume and weight related to the Wnt/-catenin and NOTCH signaling pathways. So, ESM1 is a promising biomarker for drug sensitivity, the tumor immune microenvironment, and the proliferation of cutaneous melanoma.

Machine learning algorithm-based identification and verification of characteristic genes in acute kidney injury.

BackgroundAcute kidney injury is a common renal disease with high incidence and mortality. Early identification of high-risk acute renal injury patients following renal transplant could improve their prognosis, however, no biomarker exists for early detection.MethodsThe GSE139061 dataset was used to identify hub genes in 86 DEGs between acute kidney injury and control samples using three machine learning algorithms (LASSO, random forest, and support vector machine-recursive feature elimination). We used GSEA to identify the related signal pathways of six hub genes. Finally, we validated these potential biomarkers in an in vitro hypoxia/reoxygenation injury cell model using RT-qPCR.ResultsSix hub genes (MDFI, EHBP1L1, FBXW4, MDM4, RALYL, and ESM1) were identified as potentially predictive of an acute kidney injury. The expression of ESM1 and RALYL were markedly increased in control samples, while EHBP1L1, FBXW4, MDFI, and MDM4 were markedly increased in acute kidney injury samples.ConclusionWe screened six hub genes related to acute kidney injury using three machine learning algorithms and identified genes with potential diagnostic utility. The hub genes identified in this study might play a significant role in the pathophysiology and progression of AKI. As such, they might be useful for the early diagnosis of AKI and provide the possibility of improving the prognosis of AKI patients.

Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A.

During vascular development, endothelial cAMP-dependent protein kinase A (PKA) regulates angiogenesis by controlling the number of tip cells, and PKA inhibition leads to excessive angiogenesis. Whether this role of endothelial PKA is restricted to embryonic and neonatal development or is also required for vascular homeostasis later on is unknown. Here, we show that perinatal (postnatal days P1–P3) of later (P28–P32) inhibition of endothelial PKA using dominant-negative PKA expressed under the control of endothelial-specific Cdh5-CreERT2 recombinase (dnPKAiEC mice) leads to severe subcutaneous edema, hypoalbuminemia, hypoglycemia and premature death. These changes were accompanied by the local hypersprouting of blood vessels in fat pads and the secondary enlargement of subcutaneous lymphatic vessels. Most noticeably, endothelial PKA inhibition caused a dramatic disorganization of the liver vasculature. Hepatic changes correlated with decreased gluconeogenesis, while liver albumin production seems to be unaffected and hypoalbuminemia is rather a result of increased leakage into the interstitium. Interestingly, the expression of dnPKA only in lymphatics using Prox1-CreERT2 produced no phenotype. Likewise, the mosaic expression in only endothelial subpopulations using Vegfr3-CreERT2 was insufficient to induce edema or hypoglycemia. Increased expression of the tip cell marker ESM1 indicated that the inhibition of PKA induced an angiogenic response in the liver, although tissue derived pro- and anti-angiogenic factors were unchanged. These data indicate that endothelial PKA is a gatekeeper of endothelial cell activation not only in development but also in adult homeostasis, preventing the aberrant reactivation of the angiogenic program.

P2Y2R-Mediated PAK1 Activation Is Involved in ESM-1 Overexpression in RT-R-MDA-MB-231 through FoxO1 Regulation.

Simple SummaryRadiotherapy is an important treatment to treat triple-negative breast cancer (TNBC; ER−, PR−, HER2−) patients. However, the radioresistance of BC cells remains the main obstacle to radiotherapy efficacy, which leads to increased tumor relapse and metastasis. Previously, we discovered that endothelial cell-specific molecule-1 (ESM-1) is the most increased gene in radiotherapy-resistant (RT-R)-TNBC cells compared to their parental cells and determined that ESM-1 plays a critical role in the tumorigenesis of RT-R-TNBC cells through the regulation of several genes related to tumor growth, progression and metastasis. Therefore, in this study, we aim to identify the mechanism by which ESM-1 is overexpressed in RT-R-MDA-MB-231 cells. Our results demonstrate, for the first time, that ESM-1 overexpressed in RT-R-MDA-MB-231 cells is regulated through the P2Y2R-PAK1-FoxO1 signaling pathway. Our findings suggest that targeting this pathway may be a new therapeutic target for patients with TNBC who acquire RT-R and may improve their prognosis.ESM-1, overexpressed in several cancer types, is a potential cancer diagnostic and prognostic indicator. In our previous study, we determined that RT-R-TNBC cells were more aggressive than TNBC cells, and this difference was associated with ESM-1 overexpression. However, the mechanism explaining upregulated ESM-1 expression in RT-R-TNBC cells compared to TNBC cells was unclear. Therefore, we aimed to identify the mechanism by which ESM-1 is overexpressed in RT-R-MDA-MB-231 cells. RT-R-MDA-MB-231 cells were treated with various ESM-1 transcription factor inhibitors, and only the FoxO1 inhibitor downregulated ESM-1 expression. FoxO1 nuclear localization was modulated by JNK and p38 MAPKs, which were differentially regulated by PKC, PDK1 and PAK1. PAK1 profoundly modulated JNK and p38 MAPKs, whereas PKC and PDK1 affected only p38 MAPK. P2Y2R activated by ATP, which is highly released from RT-R-BC cells, was involved in PAK1 activation, subsequent JNK and p38 MAPK activation, FoxO1 induction, and ESM-1 expression in RT-R-MDA-MB-231 cells. These findings suggest for the first time that ESM-1 was overexpressed in RT-R-MDA-MB-231 cells and regulated through the P2Y2R-PAK1-FoxO1 signaling pathway.

Biliverdin modulates the long non-coding RNA H19/microRNA-181b-5p/endothelial cell specific molecule 1 axis to alleviate cerebral ischemia reperfusion injury

Injuries caused by cerebral ischemia reperfusion (CIR) can worsen neurological outcomes, Biliverdin (BV) is an antioxidant and anti-apoptotic agent that was shown to affect CIR, although the underlying mechanisms remain unclear. In this study, we investigated the role of BV and its potential underlying mechanism in CIR injury. CIR rat models and primary cortical neurons were established and treated with and without BV. Additionally, adenovirus vectors that could overexpress LncRNA H19 and overexpress or knock-down miR-181b-5p and Esm1 were created to investigate their regulation of molecular expression. Our findings showed that BV could significantly improve CIR injury, both in vivo and in vitro, decrease LncRNA H19 and Esm1 expression, and increase miR-181b-5p expression. Overexpression of LncRNA H19 inhibited the anti-injury effects of BV. Further, the down-regulation of miR-181b-5p or up-regulation of Esm1 expression weakened the in vitro protective effect of BV. RNA immunoprecipitation assay and dual luciferase reporter gene assay further confirmed that LncRNA H19 could sponge miR-181b-5p, and Esm1 was the target of miR-181b-5p. Rescue experiments confirmed that BV could regulate the LncRNA H19/miR-181b-5p/Esm1 molecular axis. Lastly, proteomic and bioinformatic analyzes revealed that Esm1 upregulation in BV-treated neurons resulted in the differential expression of 16 proteins, including 9 upregulated and 7 downregulated proteins. In conclusion, this study found that BV could ameliorate CIR injury by regulating the LncRNA H19/miR-181b-5p/Esm1 axis.

Screening diagnostic markers for acute myeloid leukemia based on bioinformatics analysis.

BackgroundAn in-depth understanding of the key molecules and associated mechanisms involved in acute myeloid leukemia (AML) carcinogenesis, proliferation, and relapse is critical. This provides a basis for disease screening, early diagnosis, and development of effective treatment strategies and prognosis.MethodsWe downloaded AML transcription data sets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were screened by R software and limma packages. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEGs by public databases. In the DEG set, a random forest algorithm was used to identify characteristic genes of AML. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy of selected characteristic genes, which provided clues for the discovery of early diagnostic markers. The Estimate score was calculated using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. Spearman’s correlation test was used to explore the correlation between characteristic genes and Estimate Score, which provided clues for clarifying the potential pathogenic mechanism of key genes.ResultsA total of 1,494 DEGs were identified from AML samples and normal samples, among which 1,181 genes were upregulated and 313 genes were downregulated in AML. There were 2 genes with a mean decrease Gini >2, namely, CDC20 and ESM1, respectively. The ROC curve showed that the area under the curve (AUC) of CDC20 was 0.966, and the 95% confidence interval (CI) was (0.939 to 0.987) (P<0.001). The AUC of ESM1 was 0.905, and 95% CI: 0.849 to 0.953 (P<0.001). Correlation analysis showed that CDC20 expression was negatively correlated with Estimate Score (R=−0.21, P=0.0036) in AML. The expression of ESM1 was negatively correlated with Estimate Score (R=−0.57, P<0.001).ConclusionsThe genes CDC20 and ESM1 were identified as AML characteristic genes by random forest algorithm. Both CDC20 and ESM1 have good diagnostic efficacy for AML. They may play a carcinogenic role by promoting tumor cell proliferation and inhibiting immune cell chemotaxis, which are potential biological markers.

DNA Methylation and Gene Expression in Blood and Adipose Tissue of Adult Offspring of Women with Diabetes in Pregnancy-A Validation Study of DNA Methylation Changes Identified in Adolescent Offspring.

Maternal gestational diabetes and obesity are associated with adverse outcomes in offspring, including increased risk of diabetes and cardiovascular diseases. Previously, we identified a lower DNA methylation degree at genomic sites near the genes ESM1, MS4A3, and TSPAN14 in the blood cells of adolescent offspring exposed to gestational diabetes and/or maternal obesity in utero. In the present study, we aimed to investigate if altered methylation and expression of these genes were detectable in blood, as well in the metabolically relevant subcutaneous adipose tissue, in a separate cohort of adult offspring exposed to gestational diabetes and obesity (O-GDM) or type 1 diabetes (O-T1D) in utero, compared with the offspring of women from the background population (O-BP). We did not replicate the findings of lower methylation of ESM1, MS4A3, and TSPAN14 in blood from adults, either in O-GDM or O-T1D. In contrast, in adipose tissue of O-T1D, we found higher MS4A3 DNA methylation, which will require further validation. The adipose tissue ESM1 expression was lower in O-GDM compared to O-BP, which in turn was not associated with maternal pre-pregnancy BMI nor the offspring’s own adiposity. Adipose tissue TSPAN14 expression was slightly lower in O-GDM compared with O-BP, but also positively associated with maternal pre-pregnancy BMI, as well as offspring’s own adiposity and HbA1c levels. In conclusion, the lower DNA methylation in blood from adolescent offspring exposed to GDM could not be confirmed in the present cohort of adult offspring, potentially due to methylation remodeling with increased aging. In offspring adipose tissue, ESM1 expression was associated with maternal GDM, and TSPAN14 expression was associated with both maternal GDM, as well as pre-pregnancy BMI. These altered expression patterns are potentially relevant to the concept of developmental programming of cardiometabolic diseases and require further studies.

Effect of different LED lights on aliphatic glucosinolates metabolism and biochemical characteristics in broccoli sprouts

In this study, various LED lights (white, red, yellow, green, blue and purple) were applied to evaluate their effects on the biochemical parameters, aliphatic glucosinolates synthesis and sulforaphane formation in broccoli sprouts. The length of broccoli sprouts and bulk water content were decreased after LED light treatments, especially white, green, and purple LED lights. The highest contents of ascorbic acid and anthocyanins were recorded in blue LED light treated broccoli sprouts. Green LED light treated sprouts contained the highest contents of ATP, ADP and AMP. Yellow and bule lights resulted in higher glucose content. Yellow, blue, and purple LED lights induced glucoraphanin and glucoerucin accumulation via upregulating aliphatic glucosinolates biosynthetic genes. Yellow LED light caused higher glucoraphanin content than blue LED light, while sulforaphane formation showed no difference; which might be attributed to higher myrosinase activity and its expression as well as lower ESM1 expression under blue LED light.

The effects of Anisodamine-Tirofiban Combined Therapy in acute myocardial infarction treated with Percutaneous Coronary Intervention (PCI).

Objectives:To study the effects of anisodamine-tirofiban combined therapy on cardiac function and serological expression of serum NGF and ESM-1 in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI).Methods:Eighty patients with myocardial infarction treated in Cangzhou Medical College, Hebei, China from February 2015 to April 2017 were selected and divided into the control group and the research group according to the principle of random draw, 40 patients per group. The patients in the control group received symptomatic routine treatment, while the patients in the research group received anisodamine-tirofiban combined therapy on the top of symptomatic routine treatment. Differences between the two groups in TIMI flow grades, cardiac function, levels of NGF and ESM-1 and adverse response were observed.Results:The recovery of cardiac function in the research group was statistically significant with P value (p<0.05) and better than the control group in TIMI flow grades, myocardial perfusion capacity and cardiac function. The serological indicators in the research group had a higher level of NGF and a lower level of ESM-1 than the control group, and the differences were statistically significant (p<0.05). In terms of safety, neither group showed significant hepatorenal disorders.Conclusion:The combined treatment of anisodamine-tirofiban in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) can recover NGF and ESM-1 related proteins, improve postoperative myocardial perfusion, and accelerate the recovery of cardiac function. It is worth promoting in clinic.

The Regulatory Effect of miR-126-3p Exosomes Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Targeting Endothelial Cell Specific Molecule 1 on Gastric Cancer

Exosomes can transmit microRNAs (miRNAs) and other substances between different cells. Bone marrow mesenchymal stem cells (BMSCs) can migrate to tumor sites. They are related to a variety of tumors, but the role of miR-126-3p exosomes derived from BMSCs in gastric cancer has not been elucidated. miR-126-3p overexpressing BMSCs were established and cell supernatant exosomes were collected followed by measuring miR-126-3p level by PCR, ESM1 expression by western blot, targeting relationship by dual luciferase gene reporter assay along with analysis of cell proliferation, invasion and apoptosis. The addition of BMSCs exosomes to gastric cancer cells reduced the miR-126-3p level, promoted ESM1 expression, and worsened the biological behaviors of tumor cells. miR-126-3p-overexpressed BMSCs exosomes promoted miR-126-3p expression, resulting in the decrease of ESM1 expression and inhibiting the further deterioration. In conclusion, BMSCs can inhibit the increase of miR-126-3p expression and ESM1 to inhibit the deterioration of biological behaviors of gastric cancer cells.

Endothelial cell-specific molecule-1 as an invasiveness marker for pituitary null cell adenoma

BackgroundEndothelial cell-specific molecule-1 (ESM-1) is a biomarker associated with tumor progression in pituitary adenoma. We specifically focused on one type of pituitary adenoma, namely null cell adenoma (NCA) and evaluated the relationship between invasion and ESM-1 expression in both vascular endothelial and adenoma tissues.MethodsTissue samples from 94 patients with pituitary NCA were obtained through microscopic transsphenoidal resection. Tumor size and invasion were determined through preoperative magnetic resonance imaging. Immunohistochemical staining was performed to detect ESM-1 expression. ESM-1 index of ≥3 was defined as high expression.ResultsSigns of invasion were observed in 46 (47.9%) of the 94 patients. Significant differences were observed in the invasion state and maximum tumor diameter between high and low expression of ESM-1 in vascular endothelial tissues (both P < 0.05). Significant positive associations were noted between ESM-1 expression in vascular endothelial tissues and tumor invasion (P = 0.002) and tumor size (P = 0.020). However, only tumor size was associated with ESM-1 expression in adenoma tissues (P = 0.016).ConclusionIn NCA, a significant positive association between tumor invasion and ESM-1 expression was observed only in vascular endothelial tissues, suggesting that tumor progression occurs mainly through ESM-1-associated mechanism.

ALDH1A3 Regulations of Matricellular Proteins Promote Vascular Smooth Muscle Cell Proliferation.

SummaryVascular smooth muscle cell (VSMC) proliferation promotes intimal hyperplasia (IH) in occluding vascular diseases. Here we identified a positive role of ALDH1A3 (an aldehyde dehydrogenase) in this pro-IH process. The expression of ALDH1A3, but not that of 18 other isoforms of the ALDH family, was substantially increased in cytokine-stimulated VSMCs. PDGF(BB) stimulated VSMC total ALDH activity and proliferation, whereas ALDH1A3 silencing abolished this effect. ALDH1A3 silencing also diminished the expression of two matricellular proteins (TNC1 and ESM1), revealing a previously unrecognized ALDH1A3 function. Loss-of-function experiments demonstrated that TNC1 and ESM1 mediated ALDH1A3's pro-proliferative function via activation of AKT/mTOR and/or MEK/ERK pathways. Furthermore, ALDH inhibition with disulfiram blocked VSMC proliferation/migration in vitro and decreased TNC1 and ESM1 and IH in angioplasty-injured rat carotid arteries. Thus, ALDH1A3 promotes VSMC proliferation at least partially through TNC1/ESM1 upregulation; dampening excessive ALDH1A3 activity represents a potential approach to IH mitigation.

Transcriptome reveals the gene expression patterns of sulforaphane metabolism in broccoli florets.

Sulforaphane is a new and effective anti-cancer component that is abundant in broccoli. In the past few years, the patterns of variability in glucosinolate content and its regulation in A. thaliana have been described in detail. However, the diversity of glucosinolate and sulforaphane contents in different organs during vegetative and reproductive stages has not been clearly explained. In this paper, we firstly investigated the transcriptome profiles of the developing buds and leaves at bolting stage of broccoli (B52) to further assess the gene expression patterns involved in sulforaphane synthesis. The CYP79F1 gene, as well as nine other genes related to glucorahpanin biosynthesis, MAM1, MAM3, St5b-2, FMO GS-OX1, MY, AOP2, AOP3, ESP and ESM1 were selected by digital gene expression analysis and were validated by quantitative real-time PCR (qRT-PCR). Meanwhile, the compositions of glucosinolates and sulforaphane were detected for correlation analysis with related genes. Finally the RNA sequencing libraries generated 147 957 344 clean reads, and 8 539 unigene assemblies were produced. In digital result, only CYP79F1, in the glucoraphanin pathway, was up-regulated in young buds but absent from the other organs, which was consistent with the highest level of sulforaphane content being in this organ compared to mature buds, buds one day before flowering, flowers and leaves. The sequencing results also presented that auxin and cytokinin might affect glucoraphanin accumulation. The study revealed that up-regulated expression of CYP79F1 plays a fundamental and direct role in sulforaphane production in inflorescences. Two genes of MAM1 and St5b-2 could up-regulated glucoraphanin generation. Synergistic expression of MAM1, MAM3, St5b-2, FMO GS-OX1, MY, ESP and ESM1 was found in sulforaphane metabolism. This study will be beneficial for understanding the diversity of sulforaphane in broccoli organs.

Effect of raltitrexed combined with irinotecan on expression of ESM-1 and IGFBP3 in serum of patients with metastatic gastric cancer

Effect of raltitrexed combined with irinotecan on expression of ESM-1 and IGFBP3 in serum of patients with metastatic gastric cancer