Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer

Cheng, Zhenyun; Dai, Lingling; Song, Yanan; Kang, Yiqing; Si, J M; Xia, Jun; Liu, Y F

doi:10.4238/2014.july.25.5

Cited by 10 publications

(9 citation statements)

References 14 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The top one was IREB2, and then in order of significance, CHRNA3, CHRNA5, HYKK and PSMA4. 28 Silencing of IREB2 in these cells has been shown to modulate the expression of iron metabolism-related genes (transferrin receptor and ferritin) 29 and injection of wild-type IREB2 in mice was shown to stimulate growth of tumor xenografts. 26 IREB2 encodes a RNA-binding protein that regulates iron levels in cells.…”

Section: Discussionmentioning

confidence: 99%

“…Alteration of iron metabolism has been observed in NSCLC 27 and iron has been shown to influence apoptosis of lung cancer cells (A549). 28 Silencing of IREB2 in these cells has been shown to modulate the expression of iron metabolism-related genes (transferrin receptor and ferritin) 29 and injection of wild-type IREB2 in mice was shown to stimulate growth of tumor xenografts. 30 Previous studies have thus demonstrated a potential biological link between IREB2 and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptome‐wide association study reveals candidate causal genes for lung cancer

Bossé

Xia

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptome‐wide association study reveals candidate causal genes for lung cancer

Bossé

Xia

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…As we do not have the methylation and expression data in the same tissue, we were not able to validate this hypothesis directly, but future integrative studies in lung tissue should elucidate this further. IREB2 gene is coding the RNA-binding protein that binds to iron-responsive elements and can regulate the expression of transferrin receptor and ferritin by changing its own protein expression and thereby regulate iron metabolism, important in pathogenesis of lung diseases [42]. It is shown that IREB2 gene interacts with MYC and MAX genes involved in the regulation of the gene transcription through epigenetic changes [43].…”

Section: Discussionmentioning

confidence: 99%

Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics

et al. 2018

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is a major health burden in adults and cigarette smoking is considered the most important environmental risk factor of COPD. Chromosome 15q25.1 locus is associated with both COPD and smoking. Our study aims at understanding the mechanism underlying the association of chromosome 15q25.1 with COPD through epigenetic and transcriptional variation in a population-based setting. To assess if COPD-associated variants in 15q25.1 are methylation quantitative trait loci, epigenome-wide association analysis of four genetic variants, previously associated with COPD (P < 5 × 10) in the 15q25.1 locus (rs12914385:C>T-CHRNA3, rs8034191:T>C-HYKK, rs13180:C>T-IREB2 and rs8042238:C>T-IREB2), was performed in the Rotterdam study (n = 1489). All four variants were significantly associated (P < 1.4 × 10) with blood DNA methylation of IREB2, CHRNA3 and PSMA4, of which two, including IREB2 and PSMA4, were also differentially methylated in COPD cases and controls (P < 0.04). Further additive and multiplicative effects of smoking were evaluated and no significant effect was observed. To evaluate if these four genetic variants are expression quantitative trait loci, transcriptome-wide association analysis was performed in 1087 lung samples. All four variants were also significantly associated with differential expression of the IREB2 3'UTR in lung tissues (P < 5.4 × 10). We conclude that regulatory mechanisms affecting the expression of IREB2 gene, such as DNA methylation, may explain the association between genetic variants in chromosome 15q25.1 and COPD, largely independent of smoking.

show abstract

“…However, overexpression of IRP1 or IRP1 C437S dramatically suppresses the growth of tumor xenografts in nude mice (Chen et al, 2007 ), providing a direct regulatory link between the IRE/IRP system and cancer. In A549 lung cancer cells, IRP2 can regulate the expression of TfR1 and ferritin by changing its own gene expression, and thereby regulating iron metabolism (Cheng et al, 2014 ). Moreover, exhaled ferritin and superoxide dismutase (SOD) have recently been recognized to play a role in lung cancerogenesis and patients’ survival (Carpagnano et al, 2012 ), implying the possibility of using them as an outcome predictor of lung cancer.…”

Section: Iron Is Implicated In a Variety Of Cancer Typesmentioning

confidence: 99%

Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities

Zhang

2014

Protein Cell

124

View full text Add to dashboard Cite

Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells. Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy. During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.

show abstract

Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer

Cited by 10 publications

References 14 publications

Transcriptome‐wide association study reveals candidate causal genes for lung cancer

Transcriptome‐wide association study reveals candidate causal genes for lung cancer

Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics

Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities

Contact Info

Product

Resources

About