Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during embryogenesis. Gain-and loss-of-function studies in several vertebrate species have demonstrated a requirement for Gbx2 in development of the anterior hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the target genes through which GBX2 exerts its effects remain obscure. Using chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq) analysis in a human prostate cancer cell line, we identified cis-regulatory elements bound by GBX2 to provide insight into its direct downstream targets. The analysis revealed more than 286 highly significant candidate target genes, falling into various functional groups, of which 51% are expressed in the nervous system. Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1, and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and USH2A, and are plausible candidates contributing to the developmental defects in Gbx2(-/-) mice. We show through gel shift analyses that sequences within the promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/-) embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates transcriptional activity through the promoter of EEF1A1, suggesting that GBX2 could also regulate gene expression indirectly via EEF1A. Taken together, our studies show that GBX2 plays a dynamic role in development and diseases.
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PMID:Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2. 2314 17

Down's syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the 'phenotypic spectrum' associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysical nature of the chr21 duplication. Besides the cognitive disruptions and dementia in DS patients other serious health problems such as atherosclerosis, altered lipogenesis, Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), autoimmune disease, various cancers including lymphoma, leukemia, glioma and glioblastoma, status epilepticus, congenital heart disease, hypotonia, manic depression, prostate cancer, Usher syndrome, motor disorders, Hirschsprung disease, and various physical anomalies such as early aging occur at elevated frequencies, and all are part of the DS 'phenotypic spectrum.' This communication will review the genetic link between these fore-mentioned diseases and a small group of just five stress-associated microRNAs (miRNAs)-that include let-7c, miRNA-99a, miRNA-125b, miRNA-155, and miRNA-802-encoded and clustered on the long arm of human chr21 and spanning the chr21q21.1-chr21q21.3 region.
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PMID:Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down's Syndrome and Trisomy-21 Linked Disease. 2868 76