scholarly journals The A Allele of the Single-Nucleotide Polymorphism rs630923 Creates a Binding Site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines

2016 ◽  
Vol 7 ◽  
Author(s):  
Nikita A. Mitkin ◽  
Alisa M. Muratova ◽  
Anton M. Schwartz ◽  
Dmitry V. Kuprash
Keyword(s):  
Single Nucleotide Polymorphism ◽  
B Cell ◽  
Binding Site ◽  
Cell Lines ◽  
Promoter Activity ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Regulatory Single Nucleotide Polymorphism Increases TERT Promoter Activity in Thyroid Carcinoma Cells

Pathobiology ◽  
2020 ◽  
Vol 87 (6) ◽  
pp. 338-344
Author(s):  
Tatsuya Hirokawa ◽  
Yuu Arimasu ◽  
Tomohiro Chiba ◽  
Yoko Nakazato ◽  
Masachika Fujiwara ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Promoter Activity ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Carcinoma Cell Lines ◽  
Thyroid Carcinoma Cell

<b><i>Background/Aim:</i></b> The telomerase reverse transcriptase (<i>TERT</i>) promoter has a regulatory single nucleotide polymorphism (rSNP), rs2853669, and occasionally shows point mutations C228T and C250T. Although C228T and C250T have been well examined to increase <i>TERT</i> promoter activity and are known as risk factors for thyroid carcinoma, the significance of rs2853669 has not been well investigated. This study aimed to clarify the influence of rs2853669 on <i>TERT</i> promoter activity in thyroid carcinoma cells. <b><i>Materials:</i></b> Seven of 8 examined thyroid cell lines had rs2853669, 5 had C228T, and 1 had C250T. <b><i>Results:</i></b> Three papillary thyroid carcinoma cell lines, harboring both rs2853669 and C228T, showed higher <i>TERT</i> mRNA expression on real-time PCR than the other cell lines. Anaplastic thyroid carcinoma cell lines, in contrast, showed variable <i>TERT</i> mRNA expression depending on the combination of rs2853669, C228T, and C250T. Luciferase assays, performed to compare the influences of rs2853669, C228T, and C250T on <i>TERT</i> promoter activity in thyroid carcinoma, showed that rs2853669, as well as C228T, increased the promoter activity, and the combination of rs2853669 and C228T increased the promoter activity even more strongly than C228T alone. <b><i>Conclusion:</i></b> We conclude that the presence of rs2853669 within the <i>TERT</i> promoter could be as significant as the C228T mutation in thyroid carcinoma.

A single nucleotide polymorphism determines protein isoform production of the human c-FLIP protein

Blood ◽  
2009 ◽  
Vol 114 (3) ◽  
pp. 572-579 ◽  
Author(s):  
Nana Ueffing ◽  
Kusum K. Singh ◽  
Andrea Christians ◽  
Christoph Thorns ◽  
Alfred C. Feller ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
B Cell ◽  
Cell Lines ◽  
Splice Site ◽  
Death Receptor ◽  
Protein Translation ◽  
Nucleotide Polymorphism ◽  
Inhibitory Protein ◽  
Single Nucleotide ◽  
B Cell Homeostasis

Abstract The cellular FLICE-inhibitory protein (c-FLIP) is a modulator of death receptor-mediated apoptosis and plays a major role in T- and B-cell homeostasis. Three different isoforms have been described on the protein level, including the long form c-FLIPL as well as 2 short forms, c-FLIPS and the recently identified c-FLIPR. The mechanisms controlling c-FLIP isoform production are largely unknown. Here, we identified by sequence comparison in several mammals that c-FLIPR and not the widely studied c-FLIPS is the evolutionary ancestral short c-FLIP protein. Unexpectedly, the decision for production of either c-FLIPS or c-FLIPR in humans is defined by a single nucleotide polymorphism in a 3′ splice site of the c-FLIP gene (rs10190751A/G). Whereas an intact splice site directs production of c-FLIPS, the splice-dead variant causes production of c-FLIPR. Interestingly, due to differences in protein translation rates, higher amounts of c-FLIPS protein compared with c-FLIPR are produced. Investigation of diverse human cell lines points to an increased frequency of c-FLIPR in transformed B-cell lines. A comparison of 183 patients with follicular lymphoma and 233 population controls revealed an increased lymphoma risk associated with the rs10190751 A genotype causing c-FLIPR expression.

scholarly journals miR-146a promotes the initiation and progression of melanoma by activating Notch signaling

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Matteo Forloni ◽  
Shaillay Kumar Dogra ◽  
Yuying Dong ◽  
Darryl Conte ◽  
Jianhong Ou ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Notch Signaling ◽  
Cell Lines ◽  
Somatic Mutation ◽  
Melanoma Cell ◽  
Human Melanoma ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Oncogenic Mutations ◽  
Melanoma Cell Lines

Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma.

scholarly journals A miRNA Binding Site Single-Nucleotide Polymorphism in the 3′-UTR Region of the IL23R Gene Is Associated with Breast Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e49823 ◽  
Author(s):  
Lihong Wang ◽  
Wei Liu ◽  
Wei Jiang ◽  
Jing Lin ◽  
Yongdong Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphism ◽  
Binding Site ◽  
Mirna Binding Site ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Michelle A. Land ◽  
Holly L. Chapman ◽  
Brionna D. Davis-Reyes ◽  
Daniel E. Felsing ◽  
John A. Allen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Subcellular Localization ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Recycling Pathway

Abstract A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level. We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro. Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines. Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR. Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus. Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele. Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele. Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.

scholarly journals Single-nucleotide Polymorphism (SNP) in β-Defensin 2 in a Japanese Population and an Effect of - 1029 SNP on Promoter Activity

2005 ◽  
Vol 2 (2) ◽  
pp. 80-84 ◽  
Author(s):  
Kaoru Kusano ◽  
Yoshihiro Abiko ◽  
Michiko Nishimura ◽  
Toshiya Arakawa ◽  
Maiko Takeshima ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Japanese Population ◽  
Promoter Activity ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide
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