A Functional Insertion/Deletion Polymorphism in the Promoter Region of the <i>NFKB1</i> Gene Increases the Risk of Papillary Thyroid Carcinoma

Wang, Xun-Li; Peng, Hong; Liang, Yundan; Sun, Ruili; Wei, Tao; Li, Zhihui; Gong, Yanping; Gong, Renmin; Liu, Feng; Zhang, Lin; Zhu, Jingqiang

doi:10.1089/gtmb.2014.0271

Cited by 15 publications

(9 citation statements)

References 56 publications

(69 reference statements)

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“…Several studies suggested genetic variations of NF‐κB signaling confers increase risk for multiple cancers including NPC (Suzairi, Aizat, Aminudin, Nurfatimah, & Ankathil, ; Wang et al, ; Zhang et al, ; Zhou et al, ). Recently, whole‐exome sequencing studies from different groups consistently documented loss of function (LOF) mutations on multiple negative regulators of the NF‐κB pathway occur in nearly half of somatic NPC, including NFKBIA (Li, Chung, et al, ; Zhang, MacIsaac, et al, ; Zheng et al, ), CYLD (Li, Chung, et al, ; Zhang, MacIsaac, et al, ; Zheng et al, ), TRAF3 (Li, Chung, et al,; Zhang, MacIsaac, et al, ; Zheng et al, ), and TNFAIP3 (Zheng et al, ), NLRC5 (Li, Chung, et al, ; Zhang, MacIsaac, et al, ).…”

Section: High Prevalence Of Genetic Variants Of Nf‐κb Pathway Componementioning

confidence: 99%

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Man

Cai

et al. 2018

Journal Cellular Physiology

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Nasopharyngeal carcinoma (NPC) is a unique EBV-associated subtype of head and neck cancer, which has the highest incidence in Southern China and eastern South Asia. The interaction between genetic risk factors and environmental challenge, have been considered to contribute to the development of nasopharyngeal carcinogenesis. Constitutive activation of NF-κB signaling has been seen in NPC tissues and is associated with unfavorable prognosis. Recently, several whole exome sequencing study consistently revealed that high frequency mutations of NF-κB pathway negative regulators is common in nasopharyngeal carcinoma, which reinforce the importance of NF-κB driving oncogenesis. This review focuses on the current state of research in role of NF-κB in NPC carcinogenesis. We summarized the newly identified loss of function (LOF) mutations on NF-κB negative regulators leading to it's activation bypass LMP-1 stimulation. We discussed the critical role of NF-κB activation in immortalization and transformation of nasopharygeal epithelium. We also depicted how NF-κB signaling mediated chronic inflammation contribute to persistent EBV infection, immune evasion of EBV infected cells, metabolic reprogramming, and cancer stem cells (CSCs) formation in NPC. Lastly, we discussed the clinical resonance of targeting NF-κB for NPC precise therapy.

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Section: High Prevalence Of Genetic Variants Of Nf‐κb Pathway Componementioning

confidence: 99%

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Man

Cai

et al. 2018

Journal Cellular Physiology

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“… 8 Studies have shown the association of NF-κB1 gene with thyroid cancer, oral squamous cell carcinoma, and colorectal cancer. 9 – 11 However, there is little research on the association of NF-κB1 and gliomas. According to our previous study, NF-κB1 was highly expressed in gliomas.…”

Section: Introductionmentioning

confidence: 99%

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Yang

Chen

Wang

et al. 2017

OTT

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Glioma is one of the most common types of adult primary brain tumors, and the underlying molecular mechanisms still remain unclear. Nuclear factor-kappa B1 (NF-κB1) is involved in a variety of malignancies and is widely expressed in malignant tumors. However, the expression of NF-κB1 in different grades of glioma, the correlation between NF-κB1 and Bcl-2 expressions in gliomas, and the research between NF-κB1 and early apoptosis of glioma cells have not been reported so far. In this study, the expression level of NF-κB1 in 31 human glioma tissues and six nonneoplastic brain tissues was determined using quantitative real-time polymerase chain reaction. Results showed that the expression of NF-κB1 in human glioma tissues and glioma cell lines, SHG44 and U87, was significantly higher compared to noncancerous brain tissues and that the expression increased with increasing degrees of tumor malignancy. Similar results were demonstrated with the expression of Bcl-2 in the same human glioma specimens. Flow cytometry results showed that inhibition of NF-κB1 expression significantly promoted apoptosis of SHG44 and U87 in human glioma cells. Western blot analysis further confirmed decreased expression of Bcl-2 protein after inhibition of NF-κB1 protein expression. Taken together, NF-κB1 overexpression inhibits early apoptosis of glioma cells and high expression of NF-κB1 promotes the expression of antiapoptotic gene Bcl-2. Therefore, our study results provide a theoretical basis for antiapoptotic mechanism of tumor cells in association with NF-κB1.

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“…Prostate cancer (Zhang et al 2009, Kopp et al 2013, Cui et al 2015, Han et al 2015 rs28362491, rs2233406, rs3138053, rs28362491 Susceptibility 24:7 the rs28362491 insertion/deletion polymorphism in NFKB1 and has identified this polymorphism as a susceptibility factor for PTC (Wang et al 2015). We hypothesize that NF-κB-related genetic variants could represent important risk factors in development or clinical progression of NMTC and could improve our understanding of the mechanisms responsible for the effects of NF-κB on RAI responsiveness.…”

Section: Susceptibilitymentioning

confidence: 89%

“…References NF-κB polymorphisms Associated with Thyroid cancer (Wang et al 2015) rs28362491 Susceptibility Breast cancer (Wang et al 2014, Eskandari-Nasab et al 2016 rs28362491, rs2233406 Susceptibility (Jamshidi et al 2015) rs5996080, rs7973914, rs17243893, rs57890595…”

Section: Type Of Endocrine-related Malignancymentioning

confidence: 99%

Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma

Plantinga¹,

Petrulea

Oosting³

et al. 2017

Endocrine-Related Cancer

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The NF-κB inflammatory pathway plays a major role in cancer development and clinical progression. Activation of NF-κB signaling is promoted by NFKB1 and inhibited by NFKBIA. The present study aimed to determine the relevance of rs4648068 and rs2233406 genetic variants for non-medullary thyroid cancer (NMTC) susceptibility, progression and clinical outcome. This case-control and cohort study consists of a Romanian discovery cohort (157 patients and 258 controls) and a Dutch validation cohort (138 patients and 188 controls). In addition, patient cohorts were analyzed further for the association of genetic variants with clinical parameters. Functional studies were performed on human peripheral blood mononuclear cells. No associations were observed between the studied genetic variants and TC susceptibility. Although no statistically significant associations with clinical parameters were observed for rs4648068, the heterozygous genotype of rs2233406 was correlated with decreased radioactive iodide sensitivity requiring higher cumulative dosages to achieve clinical response. These findings were discovered in the Romanian cohort ( < 0.001) and confirmed in the Dutch cohort ( = 0.01). Functional studies revealed that this rs2233406 genotype was associated with elevated TLR4-mediated IL-1β production. In conclusion, genetic variation in, an inhibitor of NF-κB signaling, is associated with clinical response to RAI therapy and with increased production of the pro-inflammatory cytokine IL-1β, providing a potential mechanism for the observed clinical associations. These data suggest that NF-κB signaling is involved in NMTC pathogenesis and that the inflammatory tumor microenvironment could contribute to RAI resistance.

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A Functional Insertion/Deletion Polymorphism in the Promoter Region of the NFKB1 Gene Increases the Risk of Papillary Thyroid Carcinoma

Cited by 15 publications

References 56 publications

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Nuclear factor-kappa B1 inhibits early apoptosis of glioma cells by promoting the expression of Bcl-2

Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma

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