5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?

Commentary The human genome comprises the most predominant long interspersed nuclear element-1 (LINE-1) sequences, which are non-long-terminal repeat retrotransposons. The majority of LINE-1 repeats are inactivated through truncation, inversion and mutation.1 Importantly, DNA methylation attenuates the transcriptional activation, amplification and recombination of LINE-1 sequences, thereby maintaining genome stability.2 Indeed, global DNA hypomethylation has been associated with increased genomic instability and tumourigenesis, suggesting a more important role for hypomethylation in human cancers than the hypermethylation-induced downregulation of some tumour suppressor genes.3–5 LINE-1 hypomethylation has been shown to associate with the clinicogenetic features of multiple myeloma6 and chronic myeloid leukaemia,7 poor prognosis in non-small cell lung cancer,8 and with more aggressive progression of colorectal cancer (CRC).9 The full-length LINE-1 sequence (6 Kb) includes a sense promoter regulating transcription of two open reading frames...
Source: Gut - Category: Gastroenterology Authors: Tags: Commentary Source Type: research