Steroid metabolic process

About: Steroid metabolic process is a(n) research topic. Over the lifetime, 40 publication(s) have been published within this topic receiving 752 citation(s).

Voltage-Gated Na+ Channel SCN5A Is a Key Regulator of a Gene Transcriptional Network That Controls Colon Cancer Invasion

Abstract: Voltage-gated Na(+) channels (VGSC) have been implicated in the metastatic potential of human breast, prostate, and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Na(v)1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiologic recordings. Na(+) channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by small interfering RNAs (siRNA) specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, with strong Na(v)1.5 protein staining found in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process, and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion.

Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity

Abstract: The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale (PT), that overlaps Wernicke's classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the PT to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the FreeSurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan (GWAS) meta-analysis of PT asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the ‘steroid hormone receptor activity’ and ‘steroid metabolic process’ pathways. Variants in the genes and pathways identified may affect the role of the PT in language cognition.

Deep Sequencing of the Porcine Endometrial Transcriptome on Day 14 of Pregnancy

Abstract: In pigs, conceptus attachment to the uterine surface epithelium starts around Day 14 of pregnancy preceded by a pronounced vascularization at the implantation zones, initiating the epitheliochorial placentation. To characterize the complex transcriptome changes in the endometrium in the course of initial conceptus attachment, deep sequencing of endometrial RNA samples of pregnant animals (n = 4) and corresponding cyclic controls (n = 4) was performed using Illumina RNA-Seq. The obtained sequence reads were mapped to the porcine genome, and relative expression values were calculated for the analysis of differential gene expression. Statistical analysis revealed 1933 differentially expressed genes (false discovery rate 1%), 1229 with higher and 704 with lower mRNA concentration, in the samples from pregnant animals. Expression of selected genes was validated by the use of quantitative real-time RT-PCR. The RNA-Seq data were compared to results of a microarray study of bovine endometrium on Day 18 of pregnancy and additional related data sets. Bioinformatics analysis revealed for the genes with higher mRNA concentration in pregnant samples strong overrepresentation, particularly for immune-related functional terms but also for apoptosis and cell adhesion. Overrepresented terms for the genes with lower mRNA concentration in pregnant samples were related to extracellular region, ion transport, cell adhesion, and lipid and steroid metabolic process. In conclusion, RNA-Seq analysis revealed comprehensive transcriptome differences in porcine endometrium between Day 14 of pregnancy and corresponding cyclic endometrium and highlighted new processes and pathways probably involved in regulation of noninvasive implantation in the pig.

Protein profiles in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonate.

Abstract: Perfluorooctane sulfonate (PFOS) is widely distributed and persistent in the environment and in wildlife, and it has the potential for developmental toxicity. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the proteins that are differentially expressed in zebrafish embryos exposed to 0.5 mg/l PFOS until 192 h postfertilization. Two-dimensional electrophoresis coupled with mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that 69 proteins showed altered expression in the treatment group compared to the control group with either increase or decrease in expression levels (more than twofold difference). Of the 69 spots corresponding to the proteins with altered expression, 38 were selected and subjected to matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (TOF/TOF) analysis; 18 proteins were identified in this analysis. These proteins can be categorized into diverse functional classes such as detoxification, energy metabolism, lipid transport/steroid metabolic process, cell structure, signal transduction, and apoptosis. Overall, proteomic analysis using zebrafish embryos serves as an in vivo model in environmental risk assessment and provides insight into the molecular events in PFOS-induced developmental toxicity.

ChIP-seq and Functional Analysis of the SOX2 Gene in Colorectal Cancers.

Abstract: SOX2 is an HMG box containing transcription factor that has been implicated in various types of cancer, but its role in colorectal cancers (CRC) has not been studied. Here we show that SOX2 is overexpressed in CRC tissues compared with normal adjacent tissues using immunohistochemical staining and RT-PCR. We also observed an increased SOX2 expression in nucleus of colorectal cancer tissues (46%, 14/30 cases vs. 7%, 2/30 adjacent tissues). Furthermore, knockdown of SOX2 in SW620 colorectal cancer cells decreased their growth rates in vitro cell line, and in vivo in xenograft models. ChIP-Seq analysis of SOX2 revealed a consensus sequence of wwTGywTT. An integrated expression profiling and ChIP-seq analysis show that SOX2 is involved in the BMP signaling pathway, steroid metabolic process, histone modifications, and many receptor-mediated signaling pathways such as IGF1R and ITPR2 (Inositol 1,4,5-triphosphate receptor, type 2).