CPG METHYLATION

Effect Of High And Low CpG Methylation on Gene Expression

Effect Of High and Low CpG Methylation on Gene Expression

Introduction

Probably one of the pathological processes in which intensely studying the involvement of DNA methylated in cancer. Although this issue with other diseases in humans is of a meaningful review, some crucial aspects of this crucial relationship will also be discussed. The process of carcinogenesis involves a series of genetic and epigenesis alterations accumulated in the cell and eventually allow this unregulated growth (Dahlman, Kaaman, Jiao, Kere, Laakso, and Arner, 2005, pp. 3032-3034). Among the genetic changes the presence of mutations in key genes involved in regulating cell growth cycle and promote, the abnormal growth are worth mentioning. On the other hand, epigenetic phenomena, such as cytosine methylated, favor the occurrence of mutations (Gazzoli and Kolodner, 2003, pp. 7992-8007).

An imbalance in the DNA methylated pattern been particularly observed in sporadic cancers. Changes in methylated have increasingly been detected in cancer cells, including the loss of the latter normally methylated sequences (hypomethylation) and aberrant methylation of usually un-methylated sequences (hypermethylation), mainly located in CpG islands. Such changes are usually present in tumors where the result is an overall decrease in the total level of methylated. Hypomethylation and hypermethylation occur in sites, in the genome. However, these are different, which depends on the tumor cells, suggesting an unusual etiology. In addition, both defects may precede malignancy, indicating that they are not a simple consequence of the neoplastic process.

Discussion and Analysis

DNA methylated-mediated silencing of an increasing number of protein-coding tumour suppressor genes known to be involved in IGF2/H19. Therefore, the present study aimed to investigate whether epigenetic changes relevant in hrHPV-mediated cervical carcinogenesis may affect the expression microRNAs (miRNAs), as well. miRNAs, ~23 nucleotide long, non-coding RNAs, regulate expression of protein-coding genes at the posttranscriptional level by sequence base pairing in the 3' untranslated region (UTR) of the target mRNAs. Recent proteomic studies have shown that a single miRNA can regulate expression of hundreds of targets. The potential importance of miRNAs in cervical carcinogenesis, in general, underlined by a number of studies (Takai and Jones 2003, pp. 235-240). miRNA loci significantly associated with fragile sites, which are known insertion sites of HPV in IGF2/H19. In addition, even though no HPVencoded miRNAs been identified so far, HPVencoded genes were shown to influence the miRNA expression of its host cell. Altered miRNA expression found in IGF2/H19 cell lines, and/or cervical carcinomas compared to normal controls, and a number of these differentially expressed miRNAs shown to influence proliferation rates of IGF2/H19 cell lines SiHa or HeLa.

Interestingly, similar to protein-coding tumour suppressor genes, expression of a substantial number of miRNAs shown to be under epigenetic regulation. A well-known epigenetically silenced miRNA in human carcinogenesis is hsa-miR-124. DNA methylated of hsa-miR-124 first shown by Lujambio et al in colon, breast and lung cancer, as well as in leukaemia and lymphoma. Subsequent studies confirmed frequent hsa-miR-124 methylated in leukaemia affecting clinical outcome and additionally showed frequent hsa-miR-124 methylated in gastric ...