AATF and SMARCA2 are associated with thyroid volume in Hashimoto’s thyroiditis patients

Brčić, Luka; Barić, Ana; Benzon, Benjamin; Brekalo, Marko; Gračan, Sanda; Kaličanin, Dean; Škrabić, Veselin; Zemunik, Tatijana; Barbalić, Maja; Novak, Ivana; Pisac, Valdi Pešutić; Punda, Ante; Perica, Vesna Boraska

doi:10.1038/s41598-020-58457-x

Cited by 10 publications

(13 citation statements)

References 75 publications

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“…In addition, Pax-8, which was associated with the GO term 'nephron tubule formation' , participates in the pathogenetic process of AITD by regulating TG and TPO gene expression (26). SMARCA2, which is associated with vascular smooth muscle cell differentiation, is involved in apoptosis and thyroid volume in HT patients (27). Moreover, 34 signaling pathways associated with dysregulated miRNAs were identified by KEGG analysis.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis

et al. 2020

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MicroRNAs (miRNAs) have emerged as key regulators of cellular processes by suppressing target mRNAs at the posttranscriptional level. However, little is known regarding the expression of miRNAs in peripheral blood mononuclear cells (PBMCs) from Hashimoto's thyroiditis (HT) patients. Therefore, 38 HT patients and 36 healthy volunteers were enrolled in this study to identify HT-mediated changes in miRNA expression. Over 1,000 dysregulated miRNAs and their biological functions in the HT patients were identified. Among them, miR-125a-5p expression was upregulated and inversely correlated with low levels of MAF, a transcription factor that inhibits Th1 cells activity and the production of IFN-γ. Luciferase assay results demonstrated that MAF is a direct target gene of miR-125a-5p. Moreover, the proportion of circulating Th1 cells and the transcript levels of IFN-γ were increased in the HT patients. MiR-125a-5p expression positively correlated with the proportion of circulating Th1 cells and the serum concentrations of anti-thyroperoxidase antibodies in the HT patients. Interestingly, knockdown of miR-125a-5p in CD4 + T cells resulted in an elevated level of MAF but decreased the proportion of Th1 cells and the transcript level of IFN-γ in vitro. Furthermore, upregulated miR-125a-5p and IFN-γ transcript levels and downregulated MAF expression were detected in thyroid tissues from HT patients. Receiver operating characteristic (ROC) curves suggested that miR-125a-5p has a crucial role in the HT. Our results demonstrate that the elevated levels of miR-125a-5p contribute to the Th1 cells response in the HT patients and may be involved in the pathogenesis of HT.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis

et al. 2020

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“…Subjects: This is a retrospective observational study in which we used stored serum samples for vitamin D measurements, and phenotype information from HT patients and control participants from the CROHT biobank [ 34 , 35 ]. Total 25(OH)D (vitamin D in the text) was measured in 461 HT patients (92.41% females) and 176 control participants (93.75% females) by the LIAISON 25(OH) Vitamin D Total chemiluminescence immunoassay (DiaSorin, Saluggia, Italy).…”

Section: Methodsmentioning

confidence: 99%

“…Given the inconclusive results on the relationship between vitamin D and HT, we aimed to perform a comprehensive set of analyses, in a large group of clinically diagnosed HT patients and control individuals from the Croatian Biobank of HT patients (CROHT biobank) [ 34 , 35 ] to give more conclusive results on this topic. A recent systematic review of vitamin D concentrations in relation to HT [ 29 ] pointed to several moderators that contribute to patient heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Hashimoto’s Thyroiditis: Observations from CROHT Biobank

et al. 2021

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The aims of this study were to evaluate: (1) associations of vitamin D with the presence/severity of Hashimoto’s thyroiditis (HT) and (2) correlations of vitamin D with thyroid-related phenotypes. Total 25(OH)D (vitamin D in the text) was measured from stored serum samples of 461 HT patients and 176 controls from a Croatian Biobank of HT patients (CROHT). (1) Vitamin D levels, and proportions of vitamin D deficiency, were compared between HT cases and controls. HT patients were additionally divided into two groups (MILD and OVERT) to take into account HT severity. (2) Correlations between vitamin D and 10 clinical phenotypes in all HT patients and two subgroups of HT patients were tested using the Spearman correlation test. Our analyses were adjusted for age, gender, BMI, smoking status and seasonality of blood sampling. (1) No significant differences in vitamin D levels, or proportions of vitamin D deficiency, were detected between HT patients of all disease stages and controls. However, a nominally significant difference in vitamin D levels between MILD and OVERT subgroups (OR = 1.038, p = 0.023) was observed. Proportions of individuals with vitamin D deficiency during winter–spring were high: all HT cases (64.69%), MILD (60.64%), OVERT (68.7%), controls (60.79%). (2) A nominally significant negative correlation between vitamin D and TSH in all HT patients (r = −0.113, p = 0.029) and a positive correlation between vitamin D and systolic blood pressure in OVERT HT patients (r = 0.205, p = 0.025) were identified. Our study indicates that there is no association between vitamin D and HT; however, there may be a subtle decrease in vitamin D levels associated with overt hypothyroidism.

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“…A new publication on genetics has shown that the apoptosis antagonizing transcription factor (AATF) [92] is involved in thyroid disease in determining the volume of the gland in situations of thyroiditis [93] . AATF appears to regulate the anti-apoptotic effect of the unfolded protein response through transcriptional regulation of AKT1 [94] .…”

Section: An Interlude: Updating the Contribution Of Geneticsmentioning

confidence: 99%

“…These findings coincide with our previous description of the psychosomatic aspects of thyroid disease, where we found an association between magnesium deficiency and symptoms [194] . In 2020, Luka Brčić together with Ana Barić and others reported that the expression of AATF is diminished in cases of Hashimoto's thyroiditis and is associated with increased thyroid volume [93] . In the historical and experimental sections of this paper, we mentioned that increased thyroid volume has been a characteristic known for decades.…”

Section: A Concept Of Shared Resources As a General Basis Of Health Amentioning

confidence: 99%

Global view on the pathogenesis of benign thyroid disease based on historical, experimental, biochemical and genetic data, identifying the role of magnesium, selenium, coenzyme Q10 and iron in the context of the unfolded protein response and protein quality control of thyroglobulin

Moncayo¹,

Moncayo²,

J³

2020

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AATF and SMARCA2 are associated with thyroid volume in Hashimoto’s thyroiditis patients

Cited by 10 publications

References 75 publications

Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis

Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis

Vitamin D and Hashimoto’s Thyroiditis: Observations from CROHT Biobank

Global view on the pathogenesis of benign thyroid disease based on historical, experimental, biochemical and genetic data, identifying the role of magnesium, selenium, coenzyme Q10 and iron in the context of the unfolded protein response and protein quality control of thyroglobulin

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