Epigenetic regulation of prostate cancer: the theories and the clinical implications

• Published in: Asian journal of andrology Vol. 21; no. 3; pp. 279 - 290
• Main Authors: Liao, Yiji, Xu, Kexin
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer India Pvt. Ltd 01.05.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Wolters Kluwer - Medknow
• Subjects: Analysis; Androgen receptors; Antineoplastic Agents - therapeutic use; Biomarkers; Cancer therapies; Care and treatment; Control; Cyclin-dependent kinases; Deoxyribonucleic acid; Disease; DNA; DNA Methylation; Drugs; Enzymes; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Humans; Invited Review; Kinases; Male; Medical prognosis; Mutation; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Proteins; Transcription factors; United States > US; gene expression regulation; prostate cancer; androgen receptor signaling; diagnostic/prognostic/predictive biomarkers; epigenetics; epigenetic therapy
• ISSN: 1008-682X; 1745-7262
• DOI: 10.4103/aja.aja_53_18

Epigenetics is the main mechanism that controls transcription of specific genes with no changes in the underlying DNA sequences. Epigenetic alterations lead to abnormal gene expression patterns that contribute to carcinogenesis and persist throughout disease progression. Because of the reversible nature, epigenetic modifications emerge as promising anticancer drug targets. Several compounds have been developed to reverse the aberrant activities of enzymes involved in epigenetic regulation, and some of them show encouraging results in both preclinical and clinical studies. In this article, we comprehensively review the up-to-date roles of epigenetics in the development and progression of prostate cancer. We especially focus on three epigenetic mechanisms: DNA methylation, histone modifications, and noncoding RNAs. We elaborate on current models/theories that explain the necessity of these epigenetic programs in driving the malignant phenotypes of prostate cancer cells. In particular, we elucidate how certain epigenetic regulators crosstalk with critical biological pathways, such as androgen receptor (AR) signaling, and how the cooperation dynamically controls cancer-oriented transcriptional profiles. Restoration of a "normal" epigenetic landscape holds promise as a cure for prostate cancer, so we concluded by highlighting particular epigenetic modifications as diagnostic and prognostic biomarkers or new therapeutic targets for treatment of the disease.