Circulating MicroRNA Profiles as Potential Biomarkers for differentiated thyroid cancer recurrence
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE173248 | GEO | 2021/04/25
REPOSITORIES: GEO
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Project description:Circulating MicroRNA Profiles as Potential Biomarkers for differentiated thyroid cancer recurrence
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Project description:Activation of thyroid stimulating hormone receptor (TSHR) fundamentally leads to hyperthyroidism. To elucidate TSHR signaling, we conducted transcriptome analyses for hyperthyroid mice that we generated by overexpressing TSH. TSH overexpression drastically changed their thyroid transcriptome. In particular, enrichment analyses identified the cell cycle, phosphatidylinositol-3 kinase/Akt pathway, and Ras-related protein 1 pathway as possibly associated with goiter development. Regarding hyperthyroidism, Slc26a4 was exclusively upregulated with TSH overexpression among genes crucial to thyroid hormone secretion. To verify its significance, we overexpressed TSH in Slc26a4 knockout mice. TSH overexpression caused hyperthyroidism in Slc26a4 knockout mice, equivalent to that in control mice. Thus, we did not observe significant changes in known genes and pathways involved in thyroid hormone secretion with TSH overexpression. Our datasets might include candidate genes that have not yet been identified as regulators of thyroid function. Our transcriptome datasets regarding hyperthyroidism can contribute to future research on TSHR signaling.
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Project description:Thyroid hormone receptor beta (THRB) is post-translationally modified by small ubiquitin-like modifier (SUMO). To investigate the biological role of THRB sumoylation, we generated a mouse model with a mutation that disrupts sumoylation at lysine 146 (K146Q). The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin (TSH) (81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4 concentration, indicated blunted feedback regulation of TSH. TH profuction was 10-fold lower (per mg of thyroid tissue) in mutant mice compared to Wt mice.
2021-02-20 | GSE167105 | GEO
Project description:Deficiency in Krüppel-like zinc finger transcription factor, GLI-Similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and by what mechanism GLIS3-dysfunction causes hypothyroidism are unknown. In this study, we demonstrate that GLIS3 acts downstream of thyroid stimulating hormone (TSH)/TSHR and is indispensable for TSH/TSHR-mediated induction of thyroid follicular cell proliferation and thyroid hormone biosynthesis. ChIP-Seq and promoter analysis revealed that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, indicating that these genes are directly regulated by GLIS3. The repression of cell proliferation regulatory genes is due to the inhibition of TSH-mediated activation of the mTORC1/RPS6 pathway as well as direct transcriptional regulation of several cell division-related genes by GLIS3. Consequently, GLIS3-deficiency prevents the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a new and key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells, and uncovers a mechanism by which GLIS3-deficiency causes congenital hypothyroidism and prevents goiter development.
2017-08-30 | GSE103297 | GEO
Project description:Thyroid autonomy is a frequent cause of thyrotoxicosis in regions with iodine deficiency. Epidemiological data suggest that the prevalence of thyroid autonomy is not only inversely correlated with the ambient iodine supply, but that iodide may also influence the course of pre-existing thyroid autonomy with possibly different effects on thyroid growth and function. Iodine slows TSH effects on thyroid growth stimulation and this effect is more pronounced in thyrocytes with constitutive cAMP activation i.e. in thyroid autonomy. Iodine induced growth alteration in early stage thyroid autonomy is conferred by induction of apoptosis and G2/M arrest. Transcriptome analysis revealed significant modulation of gene networks relevant to cell adhesion, cadherin signalling and ion binding with more pronounced effects in constitutively active FRTL-5 cells compared to normal FRTL-5 cells. The aim was to study iodide-induced changes in global gene expression in an in vitro model of thyroid autonomy. This model makes use of FRTL-5 cells with stable expression of a constitutively activating TSH receptor mutation or wild type TSHR as a control.
2010-12-01 | E-GEOD-22118 | biostudies-arrayexpress
Project description:Graves’ disease is characterized by goiter, palpitation and exophthalmos (Merseburg’s trias). However, a few patients develop exophthalmos even though their thyroid function is normal, a condition known as euthyroid Graves’ disease (EGD). It remains unknown why these patients remain euthyroid, even though they have potent thyroid-stimulating antibody (TSAb). To investigate whether the immunoglobulins (IgGs) obtained from EGD patients elicit thyroid hormone-releasing activity (THRA), thyroid follicles obtained from Graves’ patients were cultured in agarose-coated culture dishes, and 125I incorporated into the thyroid follicles and organic 125I (mainly de novo-synthesized 125I-T3+125I-T4) released into the culture medium by TSH or purified IgGs were determined as thyroid hormone-releasing activity (THRA). This thyroid follicle culture system allows maintenance of the Wolff-Chaikoff effect, and the expression of mRNA for the sodium-iodide symporter is decreased by high concentrations of iodide (10-6-10-4M) and therapeutic concentrations of amiodarone (1-2microM). hTSH elicited THRA most efficiently at 0.4-10 microU/ml, suggesting that thyroid function is controlled within the normal range of TSH concentration (0.4-4.0 microU/ml). All IgGs obtained from hyperthyroid Graves’ patients elicited THRA equivalent to more than 4.6 microU/ml hTSH. IgGs obtained from EGD patients also had potent THRA, whereas IgGs obtained from normal subjects and Graves’ patients in complete remission had no significant THRA. When thyroid follicles from Graves’ thyroid, into which a number of lymphocytes had infiltrated, were used, only slight THRA was elicited by bTSH or Graves’ IgGs, probably due to inflammatory cytokines produced by immunocompetent cells that could not be separated during gentle centrifugation. Indeed, when thyroid follicles were cultured with autologous intrathyroidal lymphocytes, interleukin-2 completely abolished TSH-induced THRA. When thyroid follicles were cultured with inflammatory cytokines (interleukin-1, tumor-necrosis factor-alpha, or interferon-gamma), each cytokine inhibited TSH-induced THRA in a concentration-dependent manner. These cytokines at lower concentrations synergistically and completely inhibited TSH-induced THRA. Microarray analyses of thyroid follicles cultured with IL-1alpha, TNF-alpha, or INF-gamma revealed decreased expression of mRNAs for TSHR, NIS, TPO and thyroglobulin, accompanied by increased expression of mRNAs for chemokines and cytokines. These findings suggest that IgGs obtained from patients with EGD have potent THRA in vitro, whereas in vivo, these IgGs are unable to elicit biological activity in the thyroid gland. Presumably, immunocompetent cells that infiltrate the thyroid gland produce inflammatory cytokines that synergistically inhibit thyroid function. Since a similar phenomenon may occur in the retroorbital tissues, these patients may develop exophthalmos despite having a normal serum level of TSH. This data will be published in Hyperthyroidism: Etiology, Diagnosis and Treatment (editor-in-chief;Dr.Frank Clumbus,Nova Science Publishers, Inc, New York, USA) Experiment Overall Design: One conditioned experiments: control vs. IL-1 alpha 5ng/ml, cultured for 24 hours; control vs. TNF alpha 20ng/ml, cultured for 24 hours; control vs. IFN gamma 1000U/ml, cultured for 48 hours.
2009-05-01 | E-GEOD-15838 | biostudies-arrayexpress
Project description:A time-course analysis of TSH-stimulation in two rat thyroid cell lines (FRTL5 and FRT/TSHR) was performed. The expression levels of 8,784 transcripts were measured at three different time points, i.e. before (0), 30 minutes (30m) and 17 hours (17h) after TSH stimulation, by means of Affymetrix RG-U34A arrays. Keywords: Time course
2006-10-01 | GSE5115 | GEO
Project description:A time-course analysis of TSH-stimulation in two rat thyroid cell lines (FRTL5 and FRT/TSHR) was performed. The expression levels of 8,784 transcripts were measured at three different time points, i.e. before (0), 30 minutes (30m) and 17 hours (17h) after TSH stimulation, by means of Affymetrix RG-U34A arrays. Experiment Overall Design: 2 cell lines, 3 time points and 3 biological replicates per time point were analyzed
2008-06-13 | E-GEOD-5115 | biostudies-arrayexpress
Project description:We developed a novel culture system to obtain multilineage undifferentiated stem/progenitor cells from normal human thyroid tissues. This seems to be achieved by direct reprogramming of thyroid follicular cells. The objective of the study was to reveal gene expression profile of the obtained cells compared to primary thyrocytes. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin and cytokeratin-18, were cultured in a serum-free medium called SAGM containing insulin and EGF. Although the vast majority of cells died, a small proportion (~0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined, suggesting that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. Total RNAs were extracted from PT from three different samples (PT0808, PT0811 and PT0812) and corresponding SAGM-grown lines and subjected to Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray analysis
2011-04-15 | E-GEOD-24553 | biostudies-arrayexpress
Project description:A Microarray Search for Effects of Thyrotropin and Iodide on Angiogenesis Factors Objective: Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland. Design: Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH- or iodide-regulated gene expression was analyzed by cDNA microarray. Main outcome: TSH stimulated the expression of thyroglobulin, peroxidase, sodium-iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10-5M) medium, TSH-induced expression of VEGF-A, VEGF-B and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization. Conclusions: We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible anti-angiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.
2008-08-01 | GSE12244 | GEO