Polymorphic markers of lncRNA genes GAS5, MEG3, and SNHG16 affecting their expression levels in breast cancer

Abstract

Background. Recent studies have demonstrated the role of polymorphic marker associations in regulating the expression of certain lncRNA genes and their link to breast cancer progression. This study aims to analyze the role of polymorphic marker associations in altering the expression of lncRNA genes GAS5, MEG3, and SNHG16 in breast cancer.
Methods. The study included paired samples (tumor and histologically normal tissue) of surgical resection material from female patients with breast cancer, as well as breast tissue samples from deceased women with no history of oncopathology. Genotyping was performed for a group of polymorphic markers of lncRNA genes: SNHG16 rs8038 (G > A), GAS5 rs145204276 (ins/del CAAGG), GAS5 rs55829688 (T > C), MEG3 rs10132552 (T > C), and MEG3 rs7158663 (A > G). Expression levels of the lncRNA genes SNHG16, GAS5, and MEG3 were determined by quantitative PCR (qPCR); the significance of their changes was evaluated using the Mann-Whitney U test.
Results. A statistically significant (p < 0.05) decrease in the expression levels of lncRNA genes GAS5 and MEG3 was demonstrated in tumor tissue compared to the adjacent histologically normal breast tissue of the same patients. In individuals with the ins/del and del/del genotypes of the polymorphic marker rs145204276, an increase in GAS5 expression was observed regardless of the tissue type, which may be considered an aggravating factor for tumor progression, yet a favorable one during therapy. Expression levels of MEG3 in the presence of the A allele were significantly lower across different groups of women. A statistically significant (p ≤ 0.05) low expression level of the lncRNA gene MEG3 was demonstrated in individuals with the rs7158663 AA genotype in the tumor tissue of breast cancer patients.
Conclusion. Expression levels and alterations in the polymorphic loci of MEG3 and GAS5 genes are associated with breast cancer development and can be considered potential novel non-invasive breast cancer markers, although further studies on a larger sample size are required.