Aberrant DNA Methylation and Prostate Cancer

Abstract

Prostate cancer (PCa) is the most prevalent cancer, a significant contributor to morbidity and a leading cause of cancer-related death in men in Western industrialized countries. In contrast to genetic changes that vary among individual cases, somatic epigenetic alterations are early and highly consistent events. Epigenetics encompasses several different phenomena, such as DNA methylation, histone modifications, RNA interference, and genomic imprinting. Epigenetic processes regulate gene expression and can change malignancy-associated phenotypes such as growth, migration, invasion, or angiogenesis. Methylations of certain genes are associated with PCa progression. Compared to normal prostate tissues, several hypermethylated genes have also been identified in benign prostate hyperplasia, which suggests a role for aberrant methylation in this growth dysfunction. Global and gene-specific DNA methylation could be affected by environmental and dietary factors. Among other epigenetic changes, aberrant DNA methylation might have a great potential as diagnostic or prognostic marker for PCa and could be tested in tumor tissues and various body fluids (e.g., serum, urine). The DNA methylation markers are simple in nature, have high sensitivity, and could be detected either quantitatively or qualitatively. Availability of genome-wide screening methodologies also allows the identification of epigenetic signatures in high throughput population studies. Unlike irreversible genetic changes, epigenetic alterations are reversible and could be used for PCa targeted therapies.

Contribution of epigenetics in diabetic retinopathy

“…DNA methylation is catalyzed by DNA methyl transferases (Dnmts), a family with five members-Dnmt1, Dnmt2, Dnmt3a, Dnmt3b and Dnmt3L; out of which only Dnmt1, Dnmt3a and Dnmt3b are catalytically active. Dnmt3a and Dnmt3b are de novo methyltransferases, and Dnmt1 is a maintenance enzyme important in regulating tissue-specific patterns of methylated cytosine residues [21,22]. Pathological Dnmt activity and aberrant 5mC formation have been linked with neurodegeneration [23].…”

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

“…в супернатантах клеток более стабильны, чем неметилированные фрагменты. Кроме того, метилирование цитозинов может влиять на модификацию гистонов [171,172], формирование ДНК-триплексов, стабилизацию B-Z перехода [173], а также отрицательно сказываться на связывании транскрипционных факторов с ДНК и положительно -на взаимодействие белков, специфически связывающихся с метилированными участками ДНК [174][175][176].…”

“…Поскольку метилирование ДНК может приводить к модификации гистонов и изменению структуры хроматина [172], результатом этого процесса может быть изменение стабильности не только свободной ДНК, но и ДНК, циркулирующей в крови в составе нуклеосом и иных комплексов с белками. Действительно, было показано, что некоторые MBP, а также ДНК-метилтрансферазы могут привлекать деацетилазы гистонов к сайтам метилирования, что приводит к увеличению прочности нуклеосомной упаковки ДНК [188].…”

Soy Phytoestrogens on DNA Methylation in Prostate Cancer

“…Indeed, these genes are known to be hypermethylated in prostate cancer. This hypermethylation leads to the loss of their expressions and to chemotherapy-resistance of tumor cells [4,5].In order to understand the molecular mechanisms involved in the methylation reversion of DNA by phytoestrogens, a comparative study of the effect of phytoestrogens and 17β-estradiol was carried out on prostate cancer cell lines PC-3, LNCaP and DU 145 which differ in their Androgen Receptor (AR) status but share Estrogen Receptor Beta (ERβ). For this purpose, 24 genes were selected for their direct involvement in prostate cancer.…”

“…Indeed, these genes are known to be hypermethylated in prostate cancer. This hypermethylation leads to the loss of their expressions and to chemotherapy-resistance of tumor cells [4,5].…”