Dysregulated Transcriptional Control in Prostate Cancer

• Published in: International journal of molecular sciences Vol. 20; no. 12; p. 2883
• Main Authors: Baumgart, Simon J, Nevedomskaya, Ekaterina, Haendler, Bernard
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-06-2019; MDPI
• Subjects: Androgens; Binding sites; Cell growth; Cell proliferation; Chromatin; Chromosome translocations; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; enhancer RNA; Enhancers; Forkhead protein; Gene expression; gene transcription; Genomes; Isocitrate dehydrogenase; Kinases; Leukemia; Mutation; Prostate cancer; Proteins; Recruitment; Regulatory sequences; Review; RNA polymerase; single-nucleotide polymorphism; super-enhancer; Telomerase; Transcription factors; Yes-associated protein; enhancer RNA; gene transcription; prostate cancer; single-nucleotide polymorphism; super-enhancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20122883

Recent advances in whole-genome and transcriptome sequencing of prostate cancer at different stages indicate that a large number of mutations found in tumors are present in non-protein coding regions of the genome and lead to dysregulated gene expression. Single nucleotide variations and small mutations affecting the recruitment of transcription factor complexes to DNA regulatory elements are observed in an increasing number of cases. Genomic rearrangements may position coding regions under the novel control of regulatory elements, as exemplified by the
fusion and the amplified enhancer identified upstream of the
(
) gene. Super-enhancers are increasingly found to play important roles in aberrant oncogenic transcription. Several players involved in these processes are currently being evaluated as drug targets and may represent new vulnerabilities that can be exploited for prostate cancer treatment. They include factors involved in enhancer and super-enhancer function such as bromodomain proteins and cyclin-dependent kinases. In addition, non-coding RNAs with an important gene regulatory role are being explored. The rapid progress made in understanding the influence of the non-coding part of the genome and of transcription dysregulation in prostate cancer could pave the way for the identification of novel treatment paradigms for the benefit of patients.