The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk

Özbayer, Cansu; Kurt, Hülyam; Bayramoglu, Aysegul; Güneş, Hasan Veysi; Metintaş, Muzaffer; Değirmenci, İrfan; Öner, Kevser Setenay

doi:10.1007/s00011-015-0859-0

Cited by 22 publications

(25 citation statements)

References 26 publications

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“…NOD1 (also known as NOD1/CARD4 or NLRC1) is found on chromosome 7p14‐15 and expressed in both epithelial and myeloid‐derived cells . The rs5743336 variation of NOD1 gene results from the G to A transition at position 796 in exon 3 (peptide change: E266K) …”

Section: What Is Known and Objectivementioning

confidence: 99%

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Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

et al. 2016

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Section: What Is Known and Objectivementioning

confidence: 99%

“…NOD2 (also known as NOD2/CARD15 or NLRC2) is found on chromosome 16q12 and is primarily expressed by myeloid cells . The rs2066847 variant of NOD2 gene is a frameshift mutation (p.Leu1007fsX1008) resulting from an insertion of a cytosine at nucleotide position 3020 (3020insC).…”

Section: What Is Known and Objectivementioning

confidence: 99%

Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

et al. 2016

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“…Nucleotide-binding oligomerization domain 1 (NOD1) receptor, is a relatively recently described cytosolic PRR known to execute important functions in the immune system (Girardin et al, 2001, Ogura et al, 2001) by recognizing a wide range of microbes bearing the specific meso-diaminopimelic acid (meso-DAP) moiety and mediating the corresponding inflammatory response to these infectious agents (Carneiro et al, 2004). Not only is NOD1 important in host defense and autoimmune diseases, but recently, it has also been implicated in tumorigenesis for a number of cancers, including gastric cancer (Wang et al, 2012), head and neck carcinomas (Millrud et al, 2013), oral squamous cell cancer (Wang et al, 2014), prostate adenocarcinoma (Kang et al, 2012), and lung cancer (Ozbayer et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis

et al. 2020

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While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.

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“…Tatsumi et al reported that BNIP2 negatively regulates AKT prosurvival pathway through BMCC1 and induces apoptosis in human cancer cells 36. Polymorphisms of this gene were associated with various cancers, including breast cancer 37. BAG1 is a multifunctional protein with numerous targets that is implicated in the regulation of cell growth and apoptosis of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Double gene siRNA knockdown of mutant p53 and TNF induces apoptosis in triple-negative breast cancer cells

Pileczki¹,

Pop²,

Braicu³

et al. 2016

OTT

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Apoptosis is the major downregulated pathway in cancer. Simultaneous inhibition using specific small interfering RNA (siRNA) of two key player genes, p53 and TNF, is an interesting and feasible strategy when it comes to investigating various molecular pathways and biological processes in triple-negative breast cancer (TNBC), which is one of the most aggressive and therapeutically unresponsive forms of breast cancers. Our present research focuses on evaluating the impact of double p53-siRNA and TNF-siRNA knockdown at a cellular level, and also evaluating cell proliferation, apoptosis, induction of autophagy, and gene expression by using reverse transcription polymerase chain reaction array approaches. Simultaneous inhibition of p53 and TNF in Hs578T TNBC human cell line revealed a panel of up- and downregulated genes involved in apoptosis. Furthermore, the effects of double gene knockdown were validated in a second TNBC cell line, MDA-MB-231, by using reverse transcription polymerase chain reaction TaqMan assay. All our findings help in understanding the functional mechanisms of extrinsic apoptosis, cell signaling pathways, and the mechanisms involved in tumor cell survival, growth, and death in TNBC.

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The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk

Abstract: According to our data, the rs5743336 variant of the NOD1/CARD4 gene may influence the diagnosis and treatment of lung cancer, whereas the rs2066847 variant of the NOD2/CARD15 gene is not associated with lung cancer risk in the Turkish population.

Cited by 22 publications

References 26 publications

Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis

Double gene siRNA knockdown of mutant p53 and TNF induces apoptosis in triple-negative breast cancer cells

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