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

Year: 2020

Type: article

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.

Source: Molecular Cancer

DOI: 10.1186/s12943-020-01277-4

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

Institutions: Okayama University, Baylor University Medical Center, Baylor Scott & White Research Institute, The University of Tokyo, Tokyo Medical and Dental University, University of California San Diego, City Of Hope National Medical Center, City of Hope, Beckman Research Institute

Language: English

Topic: Cancer-related molecular mechanisms research

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,290

Funders: Japan Society for the Promotion of Science, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences

OpenAlex ID: W3096002368