تعامل بین LncRNAs HOTAIR و برچسب های MALAT1 در حساسیت به سرطان معده

عنوان انگليسی

Interaction between lncRNAs HOTAIR and MALAT1 tagSNPs in gastric cancer

خلاصه انگلیسی

Background: Single nucleotide polymorphisms (SNPs) are recognized well to regulate long non-coding RNAs (lncRNAs) expression directly and change their corresponding function. It is well established that the individual SNP effects have low prediction power. In contrast, SNP-SNP interactions have a large effect on the detection of the mechanism of complex diseases. We therefore aimed to investigate the SNP-SNP interactions of oncogenic lncRNAs HOTAIR and MALAT1 in relation to the risk of gastric cancer in a high-risk population in North-West Iran. Methods: Eight hundred blood samples from 400 gastric cancer patients and 400 healthy matched controls were recruited for genotyping in a hospital-based study. Results: Unlike HOTAIR variants, the MALAT1 rs619586 tagSNPs were not contributed to gastric cancer risk individually. The stratified analysis showed no significant association with clinicopathologic characteristics. However, we found evidence for the SNP-SNP interactions of HOTAIR and MALAT1 associated with the risk of gastric cancer (rs17720428 TG-rs619586 AA, OR=1.41; rs17720428 GG-rs619586 AA, OR=1.81; rs17720428 TG-rs619586 AG, OR=3.29; rs7958904 GC-rs619586 AA, OR=1.48; rs7958904 CC-rs619586 AA, OR=1.79; and rs7958904 GC-rs619586 AG, OR=2.42). More importantly, the interactions of HOTAIR rs1899663 and MALAT1 rs619586 tagSNPs strongly increased the risk of gastric cancer (rs1899663 GT-rs619586 AA, OR=2.3; rs1899663 TT-rs619586 AA, OR=5.42; rs1899663 GT-rs619586 AG, OR=5.4; and rs1899663 TT-rs619586 AG, OR=8.64; all the p-values were <0.001). Conclusion: We introduced novel SNP-SNP interactions between lncRNAs HOTAIR and MALAT1 tagSNPs associated with the high risk of gastric cancer. In-depth functional experiments are recommended to validate all assumptions with respect to the mechanism involved.

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