COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer

Urszula Oleksiewicz, Triantafillos Liloglou, Kalliopi-Maria Tasopoulou, Nikoleta Daskoulidou, John R Gosney, John K Field, George Xinarianos

Research output: Contribution to journalArticle (journal)peer-review

54 Citations (Scopus)

Abstract

PURPOSE: Collagen 1A1 (COL1A1), RNA-binding and pre-mRNA Processing Factor (PRPF40A), and Uncoupling Protein 2 (UCP2) were identified as downstream effectors of cytoglobin (CYGB), which was shown implicated in tumour biology. Although these three genes have been previously associated with cancer, little is known about their status in lung malignancies.

METHODS: Hereby, we investigated the expression and promoter methylation of COL1A1, PRPF40A, and UCP2 in 156 non-small cell lung cancer (NSCLC) and adjacent normal tissues.

RESULTS: We demonstrate that COL1A1 and PRPF40A mRNAs are significantly overexpressed in NSCLC (p < 1 × 10-4), while UCP2 exhibits a trend of upregulation (p = 0.066). Only COL1A1 promoter revealed hypermethylation in NSCLCs (36%), which was particularly evident in squamous cell carcinomas (p = 0.024) and in the tumours with moderate-to-good differentiation (p = 0.01). Transcript level of COL1A1, as well as PRPF40A and UCP2, exhibited striking association (p ≤ 0.001) with the expression of hypoxia markers. In addition, we demonstrate in lung cancer cell lines exposed to hypoxia or oxidative stress that COL1A1 transcription significantly responds to oxygen depletion, while other genes showed the modest upregulation in stress conditions.

CONCLUSION: In conclusion, our data revealed that COL1A1, UCP2, and PRPF40A are novel players implicated in the complex network of hypoxia response in NSCLC.

Original languageEnglish
Pages (from-to)1133-1141
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume143
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/analysis
  • Carcinoma, Non-Small-Cell Lung/genetics
  • Carrier Proteins/biosynthesis
  • Cell Hypoxia/physiology
  • Collagen Type I/biosynthesis
  • Collagen Type I, alpha 1 Chain
  • DNA Methylation
  • Female
  • Gene Expression Profiling
  • Humans
  • Lung Neoplasms/genetics
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic/genetics
  • Transcriptome
  • Uncoupling Protein 2/biosynthesis
  • Up-Regulation

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