The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer

Kunitoshi Shigeyasu, Shusuke Toden, Tsuyoshi Ozawa, Takatoshi Matsuyama, Takeshi Nagasaka, Toshiaki Ishikawa, Debashis Sahoo, Pradipta Ghosh, Hiroyuki Uetake, Toshiyoshi Fujiwara, Ajay Goel

Research output: Contribution to journalLetterpeer-review

Abstract

Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs (p < 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways – the TGFβ/SMAD and Wnt/β-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.

Original languageEnglish
Article number155
JournalMolecular Cancer
Volume19
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • Colorectal cancer
  • Enhancer
  • Epigenetic
  • MYC
  • PVT1
  • Prognostic marker

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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