Associations of single nucleotide polymorphisms in precursor-microRNA (miR)-125a and the expression of mature miR-125a with the development and prognosis of autoimmune thyroid diseases

Abstract

SummaryIt is important to search the biomarker to predict the development and prognosis of autoimmune thyroid diseases (AITDs) such as Hashimoto's disease (HD) and Graves' disease (GD). MicroRNA (miR) bind directly to the 3′ untranslated region of specific target mRNAs to suppress the expression of proteins, promote the degradation of target mRNAs and regulate immune response. miR-125a is known to be a negative regulator of regulated upon activation normal T cell expressed and secreted (RANTES), interleukin (IL)-6 and transforming growth factor (TGF)-β; however, its association with AITDs remains unknown. To clarify the association between AITDs and miR-125a, we genotyped the rs12976445 C/T, rs10404453 A/G and rs12975333 G/T polymorphisms in the MIR125A gene, which encodes miR125a, using direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 155 patients with GD, 151 patients with HD and 118 healthy volunteers. We also examined the expression of miR-125a in peripheral blood mononuclear cells (PBMCs) from 55 patients with GD, 79 patients with HD and 38 healthy volunteers using quantitative real-time PCR methods. We determined that the CC genotype and C allele of the rs12976445 C/T polymorphism were significantly more frequent in patients with HD compared with control subjects (P < 0·05) and in intractable GD compared with GD in remission (P < 0·05). The expression of miR-125a was correlated negatively with age (P = 0·0010) and down-regulated in patients with GD compared with control subjects (P = 0.0249). In conclusion, miR-125a expression in PBMCs and the rs12976445 C/T polymorphism were associated with AITD development and prognosis.

MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration

“…1A, rs12976445 polymorphism is located 54 bp upstream of pre-miR-125a. Although the in silico analysis indicated that rs12976445 polymorphism could alter neither the predicted secondary structure nor the predicted ΔG, the northern blot results demonstrated that the presence of the minor allele of rs12976445 polymorphism significantly changed the ratio of pre-miR-125a and mature miR-125a, suggesting that the polymorphism significantly interfered with the mature processing of the miRNA [20]. In this study, we collected 54 tissue samples genotyped as CC (n=32), CT (n=18), and TT (n=4) and performed real-time PCR and western blot analysis to determine the expression levels of the miRNA and the gene.…”

“…In addition, TP53INP1, as well as the apoptosis status of the host cells [36], has been reported to be under the control of the miRNAs [37]. Hu et al reported that rs12976445 polymorphism in the pri-miR-125a causes a significant reduction in the amount of mature miR-125 by compromising the mature processing of the miRNA, leading to less efficient inhibition of target genes, LIFR, and an increased risk of recurrent pregnancy loss in a Chinese population [20]. As shown in Fig.…”

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

“…Inoue et al found that MIR125A rs12976445 C/T was significantly associated with HD and intractable GD (131). Our recent study also proved that rs3746444 of miR-499a and rs12976445 of miR-125a-5p were associated with AITD susceptibility (153).…”

Mir-125a rs12976445 is Associated with Susceptibility to Thyroid Cancer: A Case-control Study

“…MiR-125a is recognized to be a negative regulator of Kruppel-like factor 13 (KLF13), and the tumor necrosis factor-a-induced protein 3 (TNFAIP3) prevents the production of regulated activation of normal T cell and secreted (RANTES), and stimulates the nuclear factor kappa B (NFkB) pathway. The MiR125A gene, which encodes miR-125a, is located on chromosome 19q13.41 [14].…”