Epigenetic DNA modifications upregulate SPRY2 in human colorectal cancers

Alexei J. Stuckel, Shuai Zeng, Zhen Lyu, Wei Zhang, Xu Zhang, Urszula Dougherty, Reba Mustafi, Qiong Zhang, Trupti Joshi, Marc Bissonnette, Samrat Roy Choudhury, Sharad Khare*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Conventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC). In this report, we assessed epigenetic DNA modifications that regulate SPRY2 expression in CRC. A total of 4 loci within SPRY2 were evaluated for 5mC using Combined Bisulfite Restriction Analysis (COBRA). Previously sequenced 5hmC nano-hmC seal data within SPRY2 promoter and gene body were evaluated in CRC. Combined bioinformatics analyses of SPRY2 CRC transcripts by RNA-seq/microarray and 450K methyl-array data archived in The Cancer Genome Atlas (TCGA) and GEO database were performed. SPRY2 protein in CRC tumors and cells was measured by Western blotting. Increased SPRY2 mRNA was observed across several CRC datasets and increased protein expression was observed among CRC patient samples. For the first time, SPRY2 hypomethylation was identified in adenocarcinomas in the promoter and gene body. We also revealed, for the first time, increases of 5hmC deposition in the promoter region of SPRY2 in CRC. SPRY2 promoter hypomethylation and increased 5hmC may play an influential role in upregulating SPRY2 in CRC.

Original languageEnglish (US)
Article number2632
JournalCells
Volume10
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • 5-hydroxymethylcytosine
  • CTCF transcription factor
  • Colorectal cancer
  • DNA methylation
  • Epigenetic regulation
  • SPRY2 gene expression

ASJC Scopus subject areas

  • Medicine(all)

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