Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Biochem Genet. 2022 Dec;60(6):2200-2225. doi: 10.1007/s10528-022-10216-5. Epub 2022 Mar 17.
Evidence and in silico analyses showed that TUSC7, miR-211, and Nurr1 may be involved in BC pathogenesis by ceRNET signaling axis. This study aimed to investigate the potential role of TUSC7/miR-211/Nurr1 ceRNET and rs2615499 variant as a novel cer-SNP in BC subjects. The expression assays were conducted by qPCR on tumor tissues (n = 50), tumor-adjacent normal tissues (TANTs) (n = 50), and clinically healthy control tissues (n = 50). The expression of TUSC7 and Nurr1 significantly decreased, but the level of miR-211 significantly increased in tumor tissues compared to TANTs and healthy normal tissues. Altered expression of TUSC7 and miR-211 was associated with poor prognosis of patients. The Nurr1 exhibited a double-edged sword-like activity in BC. In addition, TUSC7, Nurr1, and miR-211 expressions were significantly related to a novel BC-associated rs2615499 (A > C) located in the miR-211 binding site on Nurr1 3'-UTR. In the second part of the study, a case-control study was performed on BC patients (n = 100) and matched healthy controls (n = 100). The genomic DNA was isolated and genotyping was performed using Tetra-Primer ARMS PCR. The CC and AC genotypes were associated with higher expression levels of Nurr1 and worse outcomes of the disease. Our findings revealed that TUSC7 functions as a tumor suppressor in BC potentially via miR-211/Nurr1, which might be disturbed by the cer-SNP rs2615499. However, functional studies are needed to validate these results.
证据和计算机分析表明，TUSC7、miR-211 和 Nurr1 可能通过 ceRNET 信号轴参与 BC 的发病机制。本研究旨在探讨 TUSC7/miR-211/Nurr1 ceRNET 和 rs2615499 变体作为一种新的 cer-SNP 在 BC 患者中的潜在作用。通过 qPCR 在肿瘤组织（n=50）、肿瘤旁正常组织（TANTs）（n=50）和临床健康对照组织（n=50）中进行表达分析。与 TANTs 和健康正常组织相比，肿瘤组织中 TUSC7 和 Nurr1 的表达显著降低，而 miR-211 的水平显著升高。TUSC7 和 miR-211 的表达改变与患者的不良预后相关。Nurr1 在 BC 中表现出双刃剑样活性。此外，TUSC7、Nurr1 和 miR-211 的表达与位于 Nurr1 3'-UTR 上 miR-211 结合位点的新型 BC 相关 rs2615499（A>G）显著相关。在研究的第二部分，对 BC 患者（n=100）和匹配的健康对照（n=100）进行了病例对照研究。分离基因组 DNA 并使用 Tetra-Primer ARMS PCR 进行基因分型。CC 和 AC 基因型与 Nurr1 表达水平升高和疾病预后不良相关。我们的研究结果表明，TUSC7 在 BC 中作为一种肿瘤抑制因子发挥作用，可能是通过 miR-211/Nurr1，而 cer-SNP rs2615499 可能干扰其功能。然而，需要进行功能研究来验证这些结果。
