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5'- 区多态性调节肿瘤抑制基因 MFSD2A 的启动子活性。

A 5'-region polymorphism modulates promoter activity of the tumor suppressor gene MFSD2A.

机构信息

Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

出版信息

Mol Cancer. 2011 Jul 7;10:81. doi: 10.1186/1476-4598-10-81.

DOI:10.1186/1476-4598-10-81
PMID:21736709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3155907/
Abstract

BACKGROUND

The MFSD2A gene maps within a linkage disequilibrium block containing the MYCL1-EcoRI polymorphism associated with prognosis and survival in lung cancer patients. Survival discrepancies between Asians and Caucasians point to ethnic differences in allelic frequencies of the functional genetic variations.

RESULTS

Analysis of three single-nucleotide polymorphisms (SNPs) mapping in the MFSD2A 5'-regulatory region using a luciferase reporter system showed that SNP rs12072037, in linkage disequilibrium with the MYCL1-EcoRI polymorphism and polymorphic in Asians but not in Caucasians, modulated transcriptional activity of the MFSD2A promoter in cell lines expressing AHR and ARNT transcription factors, which potentially bind to the SNP site.

CONCLUSION

SNP rs12072037 modulates MFSD2A promoter activity and thus might affect MFSD2A levels in normal lung and in lung tumors, representing a candidate ethnically specific genetic factor underlying the association between the MYCL1 locus and lung cancer patients' survival.

摘要

背景

MFSD2A 基因位于一个连锁不平衡区域内，该区域包含与肺癌患者预后和生存相关的 MYCL1-EcoRI 多态性。亚洲人和高加索人之间的生存差异表明，功能性遗传变异的等位基因频率存在种族差异。

结果

使用荧光素酶报告基因系统分析 MFSD2A 5'-调控区的三个单核苷酸多态性（SNP），发现与 MYCL1-EcoRI 多态性连锁不平衡且在亚洲人群中多态但在高加索人群中无多态的 SNP rs12072037 调节了表达 AHR 和 ARNT 转录因子的细胞系中 MFSD2A 启动子的转录活性，该 SNP 位点可能与这些转录因子结合。

结论

SNP rs12072037 调节 MFSD2A 启动子活性，从而可能影响正常肺组织和肺癌肿瘤中 MFSD2A 的水平，代表了 MYCL1 基因座与肺癌患者生存相关的潜在种族特异性遗传因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/5719b5ebf758/1476-4598-10-81-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/92095c6ec934/1476-4598-10-81-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/109147457bb7/1476-4598-10-81-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/127601a29732/1476-4598-10-81-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/5719b5ebf758/1476-4598-10-81-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/92095c6ec934/1476-4598-10-81-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/109147457bb7/1476-4598-10-81-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/127601a29732/1476-4598-10-81-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a5/3155907/5719b5ebf758/1476-4598-10-81-4.jpg

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