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

doi:10.1007/s00432-017-2381-y

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

Medical School

Research output: Contribution to journal › Article (journal) › peer-review

59 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 language	English
Pages (from-to)	1133-1141
Number of pages	9
Journal	Journal of Cancer Research and Clinical Oncology
Volume	143
Issue number	7
DOIs	https://doi.org/10.1007/s00432-017-2381-y
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00432-017-2381-y

Cite this

@article{3ccf1bdb7bb743318551eb826134aa03,

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

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.",

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",

author = "Urszula Oleksiewicz and Triantafillos Liloglou and Kalliopi-Maria Tasopoulou and Nikoleta Daskoulidou and Gosney, {John R} and Field, {John K} and George Xinarianos",

year = "2017",

month = jul,

day = "1",

doi = "10.1007/s00432-017-2381-y",

language = "English",

volume = "143",

pages = "1133--1141",

journal = "Journal of Cancer Research and Clinical Oncology",

issn = "0171-5216",

publisher = "Springer Verlag",

number = "7",

}

TY - JOUR

T1 - COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer

AU - Oleksiewicz, Urszula

AU - Liloglou, Triantafillos

AU - Tasopoulou, Kalliopi-Maria

AU - Daskoulidou, Nikoleta

AU - Gosney, John R

AU - Field, John K

AU - Xinarianos, George

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor/analysis

KW - Carcinoma, Non-Small-Cell Lung/genetics

KW - Carrier Proteins/biosynthesis

KW - Cell Hypoxia/physiology

KW - Collagen Type I/biosynthesis

KW - Collagen Type I, alpha 1 Chain

KW - DNA Methylation

KW - Female

KW - Gene Expression Profiling

KW - Humans

KW - Lung Neoplasms/genetics

KW - Male

KW - Middle Aged

KW - Polymerase Chain Reaction

KW - Promoter Regions, Genetic/genetics

KW - Transcriptome

KW - Uncoupling Protein 2/biosynthesis

KW - Up-Regulation

U2 - 10.1007/s00432-017-2381-y

DO - 10.1007/s00432-017-2381-y

M3 - Article (journal)

C2 - 28258342

SN - 0171-5216

VL - 143

SP - 1133

EP - 1141

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

IS - 7

ER -

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

Abstract

Keywords

UN SDGs

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