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.

[Objective] To investigate the variation of Q promoter (Qp) in nasopharyngeal carcinoma (NPC) cells, and to compare the existing two mutant sites [62 225 site(g→a)and 62 422 site (g→c) ] Qp in NPC cells with the Qp in B95.8 cell line in the functional and biological difference. [Methods] The Qp sequence was amplified in the samples from 29 cases of paraffin-embedded tissues of NPC suffers and 14 cases of peripheral blood of healthy adults by polymerase chain reaction (PCR) method (totally 43 cases). The point mutations on specified sites were analyzed and statistically compared from sequencing results. The sequences of variant and prototype Qp were amplified by PCR and cloned into luciferase reporter vector (pGL3-basic), then transfected into HaCat cells respectively. The transcriptional activity was compared between variant and prototype Qp using luciferase reporter system. The DNA binding affinity of mutant and prototype Qp to Sp1 was compared through chromatin immunoprecipitation (CHIP) method since mutation of nt 62 225 located in a Spl binding site. [Results] The mutation rate of Qp was significantly higher in NPC compared with healthy controls (P=0.039 5, <0.05), which suggested the variant Qp was closely associated with NPC. The transcription of the luciferase gene promoted by variant Qp was significant more than that of prototype Qp in transient transfection assay (2.5:1, P<0.05). The binding affinity of variant Qp to Sp1 was about 1.52 times higher than that of prototype Qp as determined by quantitative ChIP assay. [Conclusions] The transcriptional activity was enhanced in variant Qp in NPC cells compared with prototype, which possibly through the higher binding affinity to Sp1. We suggest that the mutated Qp may play an important role during the EBV infection and transformation of nasopharyngeal epithelium.

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.
Antineoplastic Agents/therapeutic use* ; DNA Methylation ; Epigenesis, Genetic/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Humans ; Male ; Prostatic Neoplasms/genetics*