The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cance
- PDF / 2,220,476 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 88 Downloads / 155 Views
LETTER TO THE EDITOR
Open Access
The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising riskstratification biomarker in colorectal cancer Kunitoshi Shigeyasu1,2, Shusuke Toden1, Tsuyoshi Ozawa1,3, Takatoshi Matsuyama1,4, Takeshi Nagasaka2, Toshiaki Ishikawa4, Debashis Sahoo5, Pradipta Ghosh6, Hiroyuki Uetake4, Toshiyoshi Fujiwara2 and Ajay Goel1,7*
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/βCatenin 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. Keywords: PVT1, MYC, Enhancer, Epigenetic, Prognostic marker, Colorectal cancer
Main text Accumulating evidence indicates that the pathogenesis of colorectal cancer (CRC) is influenced by epigenetic modifications. Among these, in the past decade, alterations in enhancer elements have garnered a significant attention [1], and are emerging as important players in cancer pathogenesis and being exploited as potential therapeutic targets. Recently, the FANTOM5 (Functional Annotation of the Mammalian Genome 5) project * Correspondence: [email protected] 1 Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA 7 Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, 1218 S. Fifth Avenue, Suite 2226, Duarte, CA, USA Full list of author information is available at the end of the article
curated a genome-wide enhancer element atlas from normal tissues and tumor cells, using the cap analysis gene expression (CAGE) and next-generation sequencing (NGS) approaches [2–5]. Herein, we systematically examined the FANTOM5 database and identified the PVT1 locus as an epigenetic enhancer in CRC and provided a novel evidence for its role in
Data Loading...
