A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility.
- Author:
Se Lyun YOON
1
;
Yun Gil ROH
;
In Sun CHU
;
Jeonghoon HEO
;
Seung Il KIM
;
Heekyung CHANG
;
Tae Hong KANG
;
Jin Woong CHUNG
;
Sang Seok KOH
;
Vladimir LARIONOV
;
Sun Hee LEEM
Author Information
- Publication Type:Original Article
- MeSH: Alleles; Clone Cells; Cloning, Organism; CpG Islands; DNA; Gene Expression*; Luciferases; Lung Neoplasms*; Lung*; Minisatellite Repeats*; Promoter Regions, Genetic
- From:Experimental & Molecular Medicine 2016;48(7):e246-
- CountryRepublic of Korea
- Language:English
- Abstract: Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case–control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02–4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer.
