Pathway analysis of genome-wide association study on serum prostate-specific antigen levels

Ge, Yu‐Zheng; Xu, Zheng; Xu, Luwei; Peng, Yu; Zhao, Yan; Hui, Xin; Wu, Rongqian; Tan, Shengshun; Song, Qun; Wu, Jianping; Li, Wencheng; Zhu, Jun; Jia, Ru

doi:10.1016/j.gene.2014.08.044

Cited by 15 publications

(10 citation statements)

References 42 publications

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“…Enhanced expression of the 2Fe-2S protein NAF-1 is associated with the onset and progression of multiple cancer types (10,11,(14)(15)(16)(17)(18)(19). To determine whether elevated NAF-1 levels play a direct role in tumor development, we stably overexpressed NAF-1 in MDA-MB-231 cells [NAF-1(+)] and generated xenograft tumors in nude mice.…”

Section: Naf-1 Overexpression Results In a Dramatic Augmentation In Xmentioning

confidence: 99%

“…Taken together, our findings suggest that any drastic change in the lability of the NAF-1 cluster would impair its function in maintaining the levels of iron and ROS in mitochondria under control. Altering NAF-1 cluster lability via different drugs could therefore be used to treat different cancers that depend on NAF-1 overexpression for their proliferation (10,11,(14)(15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…1). Furthermore, they provide a mechanistic foundation for the role of NAF-1 overexpression in multiple cancer types, including breast (10,11), prostate (15), gastric (16), cervical (17), liver (18), and laryngeal cancers (19).…”

Section: Discussionmentioning

confidence: 99%

“…Enhanced expression of NAF-1 or mNT is associated with different cancers, including breast (10,11,14), prostate (15), gastric (16), cervical (17), liver (18), and laryngeal cancer (19). Silencing of mNT or NAF-1 expression in breast (10,11) or gastric (16) cancer cells significantly inhibited cellular proliferation and tumorigenicity, whereas overexpression of mNT in breast (14) or Significance Elevated expression of the iron-sulfur (Fe-S) protein nutrientdeprivation autophagy factor-1 (NAF-1) is associated with the progression of multiple cancer types.…”

mentioning

confidence: 99%

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Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters

Darash-Yahana

Pozniak

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

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Iron-sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the NAF-1 cluster, NAF-1(H114C), in xenograft breast cancer tumors results in a dramatic decrease in tumor size that is accompanied by enhanced mitochondrial iron and reactive oxygen accumulation and reduced cellular tolerance to oxidative stress. Furthermore, treating breast cancer cells with pioglitazone that stabilizes the 3Cys-1His cluster of NAF-1 results in a similar effect on mitochondrial iron and reactive oxygen species accumulation. Taken together, our findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. Cluster transfer reactions mediated by the overexpressed NAF-1 protein are therefore critical for inducing oxidative stress tolerance in cancer cells, leading to rapid tumor growth, and drugs that stabilize the NAF-1 cluster could be used as part of a treatment strategy for cancers that display high NAF-1 expression.Fe-S | ROS | NEET | cancer | NAF-1

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Section: Naf-1 Overexpression Results In a Dramatic Augmentation In Xmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters

Darash-Yahana

Pozniak

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

View full text Add to dashboard Cite

show abstract

“…Although large-scale GWASs have been conducted on complex diseases, including ESCC, several genetic components that contribute to ESCC variations remain ambiguous. One of the key challenges in GWAS data interpretation is the identification of causative SNPs and provision of evidence and hypothetical mechanisms responsible for the observed traits (Ge et al, 2014; Lee et al, 2014). Thus, new methods have been applied to study the existing GWAS data that may provide additional biological insights and highlight new candidate genes.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

Yang

Zhu

Qin

et al. 2015

Gene

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This study was designed to identify candidate single-nucleotide polymorphisms (SNPs) that may affect the susceptibility to esophageal squamous cell carcinoma (ESCC) and elucidate their potential mechanisms to generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset for ESCC, which included 453,852 SNPs from 1898 ESCC patients and 2100 control subjects of Chinese population, was reviewed. The identify candidate causal SNPs and pathways (ICSNPathway) analysis identified seven candidate SNPs, five genes, and seven pathways, which together revealed seven hypothetical biological mechanisms. The three strongest hypothetical biological mechanisms were as follows: rs4135113 → TDG → BASE EXCISION REPAIR; rs1800450 → MBL2 → MONOSACCHARIDE BINDING; and rs3769823 → CASP8 → d4gdiPathway. The GWAS dataset was evaluated using the ICSNPathway, which showed seven candidate SNPs, five genes, and seven pathways that may contribute to the susceptibility of patients to ESCC.

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CISD2 plays a role in age-related diseases and cancer

Liao

Zhang

2021

Biomedicine & Pharmacotherapy

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Pathway analysis of genome-wide association study on serum prostate-specific antigen levels

Cited by 15 publications

References 42 publications

Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters

Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters

Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

CISD2 plays a role in age-related diseases and cancer

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