5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?
Year: 2013
Type: article
Abstract: 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 and an antisense promoter (ASP) in the 5′-untranslated region, which contains a CpG island—usually hypermethylated in normal cells—regulating transcription of adjacent genes in the opposite direction.10–12 The ASP has been reported to function as an alternative transcription start site for several proto-oncogenes, …
Source: Gut
Authors: Abbes Belkhiri, Wael El-Rifai
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2172147519