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Transcriptome sequencing showed that syndecan-3 (SDC3) was differentially expressed in high-fat and low-fat mammary epithelial cells of Chinese Holstein cows. Previous studies found that SDC3 plays an important role in inflammatory diseases and virus infection. However, those studies did not confirm whether or not the functional gene SDC3, which plays an important role in regulating milk fat metabolism, has an effect on susceptibility to breast tissue diseases. Therefore, we studied the effects of SDC3 on milk lipid metabolism and inflammation in bovine mammary epithelial cells (BMECs) and further explored the common regulatory pathway of SDC3 in both. The overexpression of SDC3 increased the contents of triglycerides and cholesterol, reduced the content of non-esterified fatty acids, inhibited the expression of inflammatory factors (IL-6, IL-1β, TNF-α and COX-2), and reduced the production of ROS in BMECs. However, silenced SDC3 had the opposite effect. Further exploring the mechanisms of SDC3, we found that SDC3 upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARG) through the AMPK/SIRT1 signal pathway to promote milk fat synthesis. It also regulated the activation of the NF-κB pathway through the AMPK/SIRT1 signal pathway, reducing the expression of inflammatory factors and ROS production, thus inhibiting the inflammatory response of BMECs. Nuclear factor kappa B subunit 1 (NF-κB p50) was an important target of SDC3 in this process. To sum up, our results showed that SDC3 coregulated milk fat metabolism and inflammation through the AMPK/SIRT1 signaling pathway. This study laid a foundation for the comprehensive evaluation of breeding value based on multi-effect functional genes in dairy cow molecular breeding. [ABSTRACT FROM AUTHOR]

Abstract Background Compared with patients who require fewer antihypertensive agents, those with apparent treatment-resistant hypertension (aTRH) are at increased risk for cardiovascular and all-cause mortality, independent of blood pressure control. However, the etiopathogenesis of aTRH is still poorly elucidated. Methods We performed a genome-wide association study (GWAS) in first cohort including 586 aTRHs and 871 healthy controls. Next, expression quantitative trait locus (eQTL) analysis was used to identify genes that are regulated by single nucleotide polymorphisms (SNPs) derived from the GWAS. Then, we verified the genes obtained from the eQTL analysis in the validation cohort including 65 aTRHs, 96 hypertensives, and 100 healthy controls through gene expression profiling analysis and real-time quantitative polymerase chain reaction (RT-qPCR) assay. Results The GWAS in first cohort revealed four suggestive loci (1p35, 4q13.2-21.1, 5q22-23.2, and 15q11.1-q12) represented by 23 SNPs. The 23 significant SNPs were in or near LAPTM5, SDC3, UGT2A1, FTMT, and NIPA1. eQTL analysis uncovered 14 SNPs in 1p35 locus all had same regulation directions for SDC3 and LAPTM5. The disease susceptible alleles of SNPs in 1p35 locus were associated with lower gene expression for SDC3 and higher gene expression for LAPTM5. The disease susceptible alleles of SNPs in 4q13.2-21.1 were associated with higher gene expression for UGT2B4. GTEx database did not show any statistically significant eQTLs between the SNPs in 5q22-23.2 and 15q11.1-q12 loci and their influenced genes. Then, gene expression profiling analysis in the validation cohort confirmed lower expression of SDC3 in aTRH but no significant differences on LAPTM5 and UGT2B4, when compared with controls and hypertensives, respectively. RT-qPCR assay further verified the lower expression of SDC3 in aTRH. Conclusions Our study identified a novel association of SDC3 with aTRH, which contributes to the elucidation of its etiopathogenesis and provides a promising therapeutic target.

Transcriptome sequencing showed that syndecan-3 (SDC3) was differentially expressed in high-fat and low-fat mammary epithelial cells of Chinese Holstein cows. Previous studies found that SDC3 plays an important role in inflammatory diseases and virus infection. However, those studies did not confirm whether or not the functional gene SDC3, which plays an important role in regulating milk fat metabolism, has an effect on susceptibility to breast tissue diseases. Therefore, we studied the effects of SDC3 on milk lipid metabolism and inflammation in bovine mammary epithelial cells (BMECs) and further explored the common regulatory pathway of SDC3 in both. The overexpression of SDC3 increased the contents of triglycerides and cholesterol, reduced the content of non-esterified fatty acids, inhibited the expression of inflammatory factors (IL-6, IL-1β, TNF-α and COX-2), and reduced the production of ROS in BMECs. However, silenced SDC3 had the opposite effect. Further exploring the mechanisms of SDC3, we found that SDC3 upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARG) through the AMPK/SIRT1 signal pathway to promote milk fat synthesis. It also regulated the activation of the NF-κB pathway through the AMPK/SIRT1 signal pathway, reducing the expression of inflammatory factors and ROS production, thus inhibiting the inflammatory response of BMECs. Nuclear factor kappa B subunit 1 (NF-κB p50) was an important target of SDC3 in this process. To sum up, our results showed that SDC3 coregulated milk fat metabolism and inflammation through the AMPK/SIRT1 signaling pathway. This study laid a foundation for the comprehensive evaluation of breeding value based on multi-effect functional genes in dairy cow molecular breeding.

Melanoma is the deadliest cutaneous malignant tumor with high risks. Though increasing evidence has widely referred to the involvement of long non-coding RNAs (lncRNAs) in the mechanism of tumor development, including melanoma, the functional roles of most lncRNAs in melanoma remain to be explored. In this study, we focus on disclosing the role of long intergenic non-protein coding RNA 1116 (LINC01116) in melanoma. Firstly, we detected LINC01116 expression through RT-qPCR. Functional analysis and animal experiments were carried out to assess the role of LINC01116 in vivo and in vitro. Western blot analysis was employed for detection of important markers regarding epithelial mesenchymal transition (EMT). In addition, RNA pulls down, RIP and luciferase reporter assays were performed to probe into the regulatory mechanism of LINC01116. LINC01116 was significantly up regulated in melanoma cells. LINC01116 deficiency abrogated cell proliferation, migration, invasion and EMT in melanoma. Moreover, LINC01116 enhanced growth differentiation factor 11 (GDF11) and syndecan 3 (SDC3) expression through sponging microRNA-3612 (miR-3612). The oncogenic role of the LINC01116/miR-3612/GDF11/SDC3 axis in melanoma was finally demonstrated. Conclusively, LINC01116 sequestered miR-3612 and targeted GDF11 and SDC3 to contribute to the progression of melanoma. [ABSTRACT FROM AUTHOR]

In the human genome, miR‐451a, miR‐144‐5p (passenger strand), and miR‐144‐3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR‐451a: P = .00305; miR‐144‐5p: P = .00128; miR‐144‐3p: P = 9.45 × 10−5). We previously reported that miR‐451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR‐144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR‐144‐5p and miR‐144‐3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR‐144‐5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2, TRIP13, ANKRD36, CENPF, NCAPG, CLEC2D, SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR‐144‐5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP, SDC3, SH2D1A, GZMH, KIF21B, TMC8, GAB3, HLA‐DPB2, PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR‐144‐5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR‐451a, miR‐144‐5p, and miR‐144‐3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis. [ABSTRACT FROM AUTHOR]

Identification of the genes and polymorphisms underlying quantitative traits, and understanding these genes and polymorphisms affect economic growth traits, are important for successful marker-assisted selection and more efficient management strategies in commercial cattle (Bos taurus) population. Syndecan-3 (SDC3), a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel regulator of feeding behavior and body weight. The aim of this study is to examine the association of theSDC3polymorphism with growth traits in Chinese Jiaxian and Qinchuan cattle breeds (). Four single nucleotide polymorphisms (SNPs: 1–4) were detected in 555 cows from three Chinese native cattle breeds by means of sequencing pooled DNA samples and polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) methods. We found one SNP (g.28362A > G) in intron and three SNPs (g.30742T > G, g.30821C > T and 33418 A > G) in exons. The statistical analyses indicated that these SNPs ofSDC3gene were associated with bovine body height, body length, chest circumference, and circumference of cannon bone (P < 0.05). The mutant-type variant was superior for growth traits; the heterozygote was associated with higher growth traits compared to wild-type homozygote. Our result confirms the polymorphisms in theSDC3gene are associated with growth traits that may be used for marker-assisted selection in beef cattle breeding programs. [ABSTRACT FROM AUTHOR]

Background: Artemin (ARTN) has been implicated in promoting oncogenicity, tumor growth and invasiveness in diverse human malignancies. However, the clinical and prognostic significance of upstream ligand binding components, potentially mediating ARTN oncogenicity, largely remain to be determined. Methods: We determined the mRNA and protein expression of three proteins demonstrated to bind ARTN, namely GFRα1, GFRα3 and Syndecan-3 (SDC3), in benign breast disease and mammary carcinoma by in situ hybridization and immunohistochemistry, respectively. Their prognostic significance combined with ARTN expression was also investigated in mammary carcinoma. Results: The expression of GFRα1 and GFRα3, but not SDC3, was significantly increased in mammary carcinoma and positively associated with tumor lymph node metastases, higher clinical stage and HER-2 positivity. Moreover, both GFRα1 and GFRα3 expression were significantly associated with survival outcome of patients with mammary carcinoma by univariate and multivariate analyses, whereas expression of SDC3 was not. Co-expression of ARTN with either GFRα1 or GFRα3, but not SDC3, produced synergistic increases in the odds ratio for both relapse-free and overall survival in patients with mammary carcinoma. Furthermore, significant association of GFRα1 and GFRα3 expression with survival outcome observed herein were restricted to ER negative or HER-2 negative mammary carcinoma. Conclusions: The expression of GFRα1 and/or GFRα3, especially when combined with ARTN expression, may be useful predictors of disease progression and outcome in specific subtypes of mammary carcinoma. [ABSTRACT FROM AUTHOR]

The role of TRPM2-AS lncRNA in OvC has not been explored. This study aimed to investigate whether and how TRPM2-AS contributes to the progression of OvC. First, qRT-PCR was employed to measure the expression of TRPM2-AS, miR-138-5p and SDC3 in OvC samples. A xenograft formation assay was subsequently performed to detect the tumor growth in vivo . The cell viability, colony formation, cell migration, cell invasion and cell apoptosis were later evaluated using a series of experiments. The western blot assay was utilized to detect the SDC3 protein expression and cell-apoptosis markers. Luciferase reporter gene assay, RIP, and RNA pull-down assays were performed to identify the association between TRPM2-AS, miR-138-5p and SDC3 . Findings indicated that the expression of TRPM2-AS and SDC3 was significantly upregulated in OvC tissues and cells, while miR-138-5p expression was significantly downregulated in OvC samples. Unlike miR-138-5p, TRPM2-AS and SDC3 were found to promote OvC development. It was also found that TRPM2-AS could sponge miR-138-5p to release SDC3 , thus promoting OvC progression. Apart from that, we discovered that both sh-TRPM2-AS and cisplatin could enhance the apoptosis of OvC cells. Overall, our findings suggested that the TRPM2-AS/miR-138-5p/ SDC3 axis was closely associated with OvC tumorigenesis and cisplatin resistance.

Background: Emerging studies have indicated that circular RNAs (circRNAs) play important roles in the development of many tumors. CircRNA-scavenger receptor class B member 1 (Circ-SCARB1) was consistently reported as an elevated circRNA in RCC tissues. This study focused on examining the biological function and molecular mechanism of circSCARB1 in RCC progression., Methods: Expressions of Circ-SCARB1, microRNA (miR)-510-5p, and syndecan 3 (SDC3) were detected using a quantitative real-time polymerase chain reaction (RT-PCR) and/or western blot. Cell proliferation and apoptosis were measured by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-diphenytetrazoliumromide and flow cytometry, respectively. Cell migration and invasion were measured using Transwell assays. The interaction between miR-510-5p and Circ-SCARB1 or SDC3 was verified using dual-luciferase reporter assays., Results: Circ-SCARB1 was elevated in 30 pairs of RCC tissues and multiple RCC cell lines. Knockdown of Circ-SCARB1 inhibited cell proliferation, migration, and invasion while inducing cell apoptosis. MiR-510-5p was confirmed to be a target of Circ-SCARB1; inhibition of cell progression by silencing Circ-SCARB1 was mediated by a direct interaction between Circ-SCARB1 and miR-510-5p. SDC3 was verified to be a gene target of miR-510-5p; transfection of miR-510-5p mimic not only suppressed the expression of SDC3 but also the cell proliferation and an SDC3 cotransfection partially restored cell proliferation. Additionally, the genetic knockdown of Circ- SCARB1 reduced the expression SDC3, and the addition of anti-miR-510-5p could partially reelevate SDC3 expression., Conclusion: Circ-SCARB1 promotes RCC progression via sequestering miR-510-5p and indirectly up-regulating SDC3 expression. This provides a novel perspective for the pathogenesis of RCC and potential therapeutic targets for the treatment of RCC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The development of the central nervous system requires an appropriate micro-environment that is conditioned by a combination of various extracellular components. Most of the known signaling factors, such as neurotransmitters or neuropeptides, are soluble and diffuse into the extracellular matrix. However, other secreted molecules like proteoglycans or glycosaminoglycans anchor in the extracellular matrix to influence cerebral ontogenesis. As such, pleiotrophin (PTN), which binds the proteoglycans syndecan-3 (SDC3) and protein tyrosine phosphatase zeta (PTPζ), has been described as a pro-migratory and a pro-differentiating secreted cytokine on cortical neurons. In rat cerebellum, PTN is highly expressed during the first postnatal week, suggesting that this cytokine could participate to the development of the cerebellar cortex. According to this hypothesis, our spatio-temporal cartography of PTN, PTPζ and SDC3 indicated that, in mouse, the PTNergic system was present in the cerebellum at least from the first postnatal day (P0). Until P12, PTN was mainly expressed by granule cell precursors and located in the extracellular matrix, while SDC3 was expressed by Purkinje cells, Golgi cells and granule cell precursors, and PTPζ was present on Purkinje cells and Bergmann fibers. In vitro studies confirmed the presence of SDC3 on immature granule cells and demonstrated that PTN could stimulate directly their velocity in culture. In contrast, subarachnoidal injection of PTN in the cerebellum significantly reduced the rate of migration of granule cells, exacerbated their apoptosis and induced an atrophy of the Purkinje cell dendritic tree. Since differentiated granule cells did not express SDC3 or PTPζ, the PTN effect observed on migration and apoptosis may be indirectly mediated by Purkinje and/or Bergmann cells. From P21 to adulthood, the distribution of PTN, SDC3 and PTPζ changed and their expression dramatically decreased even if they were still detectable. PTN and SDC3 immunolabeling was restricted around Purkinje cell bodies and Golgi cells, whereas PTPζ was located around interneurons. These data suggested that, in the cerebellum of adult mice, PTN participates to the perineuronal nets that control neuronal plasticity. To conclude, the present work represents the first spatio-temporal characterization of the PTNergic system in the mouse cerebellum and indicates that PTN may contribute to cerebellum ontogenesis during the postnatal development as well as to neuronal plasticity at adulthood., (Copyright © 2013 Elsevier Inc. All rights reserved.)