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5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?
  1. Abbes Belkhiri1,
  2. Wael El-Rifai1,2
  1. 1 Department of Surgery and Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  2. 2 Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
  1. Correspondence to Professor Wael El-Rifai and Dr Abbes Belkhiri, Department of Surgery and Department of Cancer Biology, Vanderbilt University Medical Center, 760 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232-6308, USA; wael.el-rifai{at} or abbes.belkhiri{at}

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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.35 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.1012 The ASP has been reported to function as an alternative transcription …

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  • Contributors AB: Assisted in writing a draft of the paper. WER: Wrote the final version of the paper.

  • Funding The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute, Department of Veterans Affairs or Vanderbilt University.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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