A Proposed Tusc7/Mir-211/Nurr1 Cernet Might Potentially Be Disturbed by a Cer-Snp Rs2615499 in Breast Cancer Publisher Pubmed



Abdollahzadeh R¹ ; Azarnezhad A^{2, 3} ; Paknahad S¹ ; Mansoori Y⁴ ; Pirhoushiaran M¹ ; Kanaani K⁵ ; Bafandeh N¹ ; Jafari D⁶ ; Tavakkolybazzaz J¹
Source: Biochemical Genetics Published:2022

Abstract

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. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.