Homo sapiens
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PROVIDER: PRJNA150877 | ENA |
REPOSITORIES: ENA
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Project description:Overexpression of HIP1 has been associated with fibroblast transformation, increasing grades of prostate cancer (CaP), and biochemical relapse. Here we demonstrate cellular transformation and phenotypic effects of HIP1 overexpression in a benign prostate epithelial cell line to be dependent on STAT3 signalling. In vivo xenografts confirmed the cellular transformation phenotype and revealed serum GDF15 to be a marker of CaP in our model. STAT3 signalling was in part, dependent on HIP1 expression, in a highly invasive, metastatic and androgen receptor (AR) negative DU145 cell line, Immunohistochemistry of a large prostate tissue microarray (TMA) revealed increased HIP1 and reciprocal GDF15 expression to adversely affect outcome warranting further studies to assess HIP1 and GDF15 as biomarkers for detection and prognostication of CaP. Gene expression of PNT1a cells stably overexpressing HIP1 protein and LNCaP cells transiently overexpressing HIP1 protein were compared with their respective empty vector control cell lines using the illumina expression array platform. There were six biological replicates for each of the four different groups.
2016-09-01 | E-GEOD-35211 | biostudies-arrayexpress
Project description:Overexpression of HIP1 has been associated with fibroblast transformation, increasing grades of prostate cancer (CaP), and biochemical relapse. Here we demonstrate cellular transformation and phenotypic effects of HIP1 overexpression in a benign prostate epithelial cell line to be dependent on STAT3 signalling. In vivo xenografts confirmed the cellular transformation phenotype and revealed serum GDF15 to be a marker of CaP in our model. STAT3 signalling was in part, dependent on HIP1 expression, in a highly invasive, metastatic and androgen receptor (AR) negative DU145 cell line, Immunohistochemistry of a large prostate tissue microarray (TMA) revealed increased HIP1 and reciprocal GDF15 expression to adversely affect outcome warranting further studies to assess HIP1 and GDF15 as biomarkers for detection and prognostication of CaP.
2016-09-01 | GSE35211 | GEO
Project description:Prostate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. Here, we find that genetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and anti-tumor immunity via recruitment of cytotoxic T-cells, ultimately impeding tumor progression. Our findings reveal a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.
2024-11-04 | GSE277063 | GEO
Project description:Prostate cancer is the most frequently diagnosed malignancy in adult males. Though multiple factors have been implicated in prostate cancer progression, the trigger for initiation of malignancy is still a topic of debate. Advanced age is the single most significant risk factor for prostate cancer. Epidemiological and clinical studies indicate oxidative stress as one of the major aging-associated influences on prostate carcinogenesis. In this study, for the first time, we demonstrated the intrinsic association of ROS and IL6/STAT3 in prostate carcinogenesis. The high levels of ROS/IL6/STAT3 activation in this carcinogenesis model will benefit understanding of the mechanism of prostate cancer initiation and progression, as well as therapeutic development of anti-cancer drug targeting of the IL6/STAT3 pathway.
2013-04-24 | E-MTAB-1521 | biostudies-arrayexpress
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature
Project description:PurposeWe investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level.MethodsSNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively.ResultsSix of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes.ConclusionsThere is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.
| S-EPMC3743458 | biostudies-literature
Project description:Cortical thickness has been investigated since the beginning of the 20th century, but we do not know how similar the cortical thickness profiles among humans are. In this study, the local similarity of cortical thickness profiles was investigated using sliding window methods. Here, we show that approximately 5% of the cortical thickness profiles are similarly expressed among humans while 45% of the cortical thickness profiles show a high level of heterogeneity. Therefore, heterogeneity is the rule, not the exception. Cortical thickness profiles of somatosensory homunculi and the anterior insula are consistent among humans, while the cortical thickness profiles of the motor homunculus are more variable. Cortical thickness profiles of homunculi that code for muscle position and skin stimulation are highly similar among humans despite large differences in sex, education, and age. This finding suggests that the structure of these cortices remains well preserved over a lifetime. Our observations possibly relativize opinions on cortical plasticity.
| S-EPMC5738339 | biostudies-literature