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Serum and thyroid tissue level of let-7b and their correlation with TRAb in Graves' disease
Xinxin Chen1, Fengjiao Huang1, Yicheng Qi1
1Department of Endocrinology, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University Medical School, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.
Background:
Abnormal microRNAs (miRNAs) were reported to be involved in the mechanism of Graves' disease (GD). Dysregulated miRNAs may be overlapping in different cells and can be secreted to circulation. We chose miRNAs which were previously reported to be differentially expressed in peripheral blood mononuclear cells (PBMCs) in patients with GD with different disease stage, detected the expression of those miRNAs in serum, corroborated the findings in thyroid tissue, and validated the target gene in vitro to investigate the possible role of circulating miRNAs in GD.
Methods:
A total of 54 individuals with untreated GD, 12 individuals with GD in remission and 14 disease-free controls were enrolled. The expression of miR-142-3p, miR-154-3p, miR-431-3p, miR-590-5p, and let-7b was detected in the serum. Ten thyroid tissue samples from patients with GD and six disease-free thyroid samples were used for further validation. The potential target genes were identified and validated in vitro.
Results:
miR-142-3p, miR-154-3p, miR-431-3p, miR-590-5p, and let-7b were present in serum and two of them (miR-142-3p and let-7b) were significantly increased in serum of patients with untreated GD (for serum miR-142-3p, P = 0.033, for serum let-7b, P = 0.026) and gradually decreased to normal levels in patients with GD in remission. Correlation analysis showed that let-7b level was strongly correlated with TRAb level (r = 0.305, P = 0.001). let-7b directly inhibited promyelocytic leukemia zinc finger (PLZF) expression and increased the expression of TSHR in thyroid cells in vitro. Furthermore, let-7b levels in GD thyroid tissue were found to be inversely correlated with PLZF levels (r = - 0.849, P = 0.033). Decreased PLZF and increased TSHR was validated in thyroid tissue in patients with GD.
Conclusions:
The present study confirmed that a portion of miRNAs in PBMCs were also presented and differentially expressed in serum and thyroid tissue. Upregulated in all these three compartments, let-7b may be used as a disease biomarker and therapeutic targets in patients with GD. Circulating let-7b had a strong correlation with disease severity and let-7b may participate in the production of TRAb via targeting PLZF in patients with GD.
Insights
Graves' disease (GD) involves abnormal microRNAs (miRNAs). Circulating let-7b is elevated in GD patients, correlates with disease severity, and may target PLZF, suggesting its potential as a biomarker and therapeutic target.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Abnormal microRNAs (miRNAs) are implicated in Graves' disease (GD) pathogenesis.
- Dysregulated miRNAs can be found in various cell types and secreted into circulation.
- This study investigates circulating miRNAs in GD, focusing on those previously identified in peripheral blood mononuclear cells (PBMCs).
Purpose of the Study:
- To detect and validate the expression of specific miRNAs in the serum of Graves' disease patients.
- To correlate miRNA expression with disease stage and clinical markers.
- To elucidate the in vitro function of identified miRNAs and their target genes in GD.
Main Methods:
- Serum samples from 54 untreated GD patients, 12 in remission, and 14 controls were analyzed for miRNA expression.
- Thyroid tissue samples from 10 GD patients and 6 controls were used for validation.
- In vitro experiments were conducted to validate target gene interactions.
Main Results:
- miR-142-3p and let-7b were significantly increased in the serum of untreated GD patients (P=0.033 and P=0.026, respectively).
- Serum let-7b levels decreased to normal in GD remission and strongly correlated with TRAb levels (r=0.305, P=0.001).
- let-7b directly inhibited PLZF expression and increased TSHR expression in thyroid cells, with inverse correlation in GD thyroid tissue (r=-0.849, P=0.033).
Conclusions:
- let-7b is upregulated in serum and thyroid tissue of GD patients, correlating with disease severity.
- Circulating let-7b shows potential as a biomarker for GD diagnosis and monitoring.
- let-7b may play a role in TRAb production by targeting PLZF, offering a potential therapeutic target.