Department of Biology, Faculty of Basic Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
Department of Genetics, Faculty of Medicine, Kazerun Branch, Islamic Azad University, P.O. Box: 73135-168, Kazerun, Iran.
World J Surg Oncol. 2024 May 28;22(1):142. doi: 10.1186/s12957-024-03415-4.
The high mobility group A2 (HMGA2) gene is expressed extensively during early embryonic development but is inactivated in adulthood, and it is also reactivated in various benign and malignant tumors, including breast cancer. We first assessed the potential functional significance of the unstudied deletion polymorphism rs10573247 at the 3'UTR of HMGA2 on miRNA binding using bioinformatic tools, and subsequently, the association between this polymorphism and breast cancer susceptibility was investigated.
We applied the RNAhybrid tool to predict the functional effects of polymorphism rs10573247 located within the 3' UTR of the HMGA2 gene on miRNA binding. Then, following DNA extraction, 141 breast cancer patients and 123 healthy controls were genotyped for polymorphism rs10573247 using RFLP-PCR with the restriction enzyme Eam1104I.
Our bioinformatic data have shown that polymorphism rs10573247 is located in the region that serves as a potential target site for eight miRNAs binding. Among them, miR-3125 exhibited decreased binding affinity for the allele delTT (MFE = -21.8) when compared to the allele TT (MFE = -23.9), but miR-4476 increased binding affinity for the allele delTT (MFE = -22.4) compared to the allele TT (MFE = -22.2). In addition, our results showed that the genotype TT/delTT (p = 0.005) and the genotype delTT/delTT (p = 0.029) were significantly associated with an increased risk of developing breast cancer compared to the genotype TT/TT using RFLP-PCR.
Our findings suggest that polymorphism rs10573247 may contribute to the risk of breast cancer through the functional effect of this polymorphism on miRNA binding.
高迁移率族蛋白 A2（HMGA2）基因在早期胚胎发育过程中广泛表达，但在成年后失活，并且在各种良性和恶性肿瘤中重新激活，包括乳腺癌。我们首先使用生物信息学工具评估了 HMGA2 基因 3'UTR 中未研究的缺失多态性 rs10573247 对 miRNA 结合的潜在功能意义，随后研究了该多态性与乳腺癌易感性的关系。
我们应用 RNAhybrid 工具预测位于 HMGA2 基因 3'UTR 内的多态性 rs10573247 对 miRNA 结合的功能影响。然后，在提取 DNA 后，使用 Eam1104I 限制性内切酶的 RFLP-PCR 对 141 名乳腺癌患者和 123 名健康对照者进行了多态性 rs10573247 的基因分型。
我们的生物信息学数据表明，多态性 rs10573247 位于作为八个 miRNA 结合的潜在靶位点的区域。其中，与 TT 等位基因相比，等位基因 delTT（MFE=-21.8）的 miR-3125 结合亲和力降低，但与 TT 等位基因相比，miR-4476 的结合亲和力增加delTT（MFE=-22.4）等位基因（MFE=-22.2）。此外，我们的结果表明，与 TT/TT 基因型相比，TT/delTT（p=0.005）和 delTT/delTT（p=0.029）基因型与患乳腺癌的风险显著增加有关使用 RFLP-PCR。
我们的发现表明，多态性 rs10573247 可能通过该多态性对 miRNA 结合的功能影响，导致乳腺癌的风险增加。
