Classification moléculaire des tumeurs thyroïdiennes: intérêts et limites de l'approche transcriptormique

Le transcriptome permet d\u27avoir une vision globale des fonctions dérégulées dans une classe tumorale. » L\u27analyse du transcriptome permet d\u27identifier les processus tumoraux initiaux, mais aussi les réactions du tissu environnant (infiltrats lymphocytaires). » Il existe une meilleure corrélation entre le statut mutationnel et le transcriptome d\u27une tumeur qu\u27entre le statut mutationnel et l\u27histologie de cette tumeur. » L\u27identification de biomarqueurs spécifiques de classe n\u27est pertinente que si le transcriptome de l\u27ensemble des classes pathologiques de l\u27organe est exploré. » Le profil d\u27expression de biomarqueurs ciblés présente un réel potentiel diagnostique pour les classes intermédiaires de pathologies

Phylogenetic analysis of the human thyroglobulin regions.

International audienceABSTRACT: Thyroglobulin is a large protein present in all vertebrates. It is synthesized in the thyrocytes and exported to lumen of the thyroid follicle, where its tyrosine residues are iodinated . The iodinated thyroglobulin is reintegrated into the cell and processed (cleaved to free its two extremities) for thyroid hormone synthesis. Thyroglobulin sequence analysis has identified four regions of the molecule: Tg1, Tg2, Tg3 and ChEL. Structural abnormalities and mutations result in different pathological consequences, depending on the thyroglobulin region affected. We carried out a bioinformatic analysis of thyroglobulin, determining the origin and the function of each region. Our results suggest that the Tg1 region acts as a binding protein on the apical membrane, the Tg2 region is involved in protein adhesion and the Tg3 region is involved in determining the three-dimensional structure of the protein. The ChEL domain is involved in thyroglobulin transport, dimerization and adhesion. The presence of repetitive domains in the Tg1, Tg2 and Tg3 regions suggests that these domains may have arisen through duplication

Les microARNs

MiRNAs are small non-coding RNAs ensuring the post-transcriptional regulation of gene expression. Their expression is tissue-specific and some miRNAs have diagnostic and / or prognostic value for tumor classes. MiRNAs are involved in tumorigenesis by two mechanisms: amplification or deletion of chromosomal regions containing clusters of genes encoding miRNAs (quantitative effect) or modification of the effects of miRNAs on their target genes by mutation in the region of interaction with the mRNA (qualitative effect). Their specificity, the possibility for miRNA measurement in blood, must now lead to consider miRNAs as markers for therapeutic management. A better understanding of the different regulatory mechanisms involving miRNAs will also consider new therapeutic approaches

Marked Hyperthyroxinemia During Amiodarone Treatment Revealing Thyroid Hormone Resistance Syndrome

International audienc

Estrogen-related receptor α and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria

Mitochondrial biogenesis, which depends on nuclear as well as mitochondrial genes, occurs in response to increased cellular ATP demand. The nuclear transcriptional factors, estrogen-related receptor α (ERRα) and nuclear respiratory factors 1 and 2, are associated with the coordination of the transcriptional machinery governing mitochondrial biogenesis, whereas coactivators of the peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) family serve as mediators between the environment and this machinery. In the context of proliferating cells, PGC-1-related coactivator (PRC) is a member of the PGC-1 family, which is known to act in partnership with nuclear respiratory factors, but no functional interference between PRC and ERRα has been described so far. We explored three thyroid cell lines, FTC-133, XTC.UC1 and RO 82 W-1, each characterized by a different mitochondrial content, and studied their behavior towards PRC and ERRα in terms of respiratory efficiency. Overexpression of PRC and ERRα led to increased respiratory chain capacity and mitochondrial mass. The inhibition of ERRα decreased cell growth and respiratory chain capacity in all three cell lines. However, the inhibition of PRC and ERRα produced a greater effect in the oxidative cell model, decreasing the mitochondrial mass and the phosphorylating respiration, whereas the nonphosphorylating respiration remained unchanged. We therefore hypothesize that the ERRα–PRC complex plays a role in arresting the cell cycle through the regulation of oxidative phosphorylation in oxidative cells, and through some other pathway in glycolytic cells

A Child with Resistance to Thyroid Hormone without Thyroid Hormone Receptor Gene Mutation: A 20-Year Follow-Up

We report here the 20-year follow-up study of a male subject diagnosed at 15 months of age as a sporadic case of pituitary resistance to thyroid hormone on the combination of clinical hyperthyroidism, elevated serum thyroid hormone (TH) levels and inappropriate thyrotropin (TSH). On d-thyroxine (D-T4) therapy from 30 months of age to 12.5 years, hyperactivity and hyperthyroid signs and symptoms as well as growth abnormalities improved, serum l-thyroxine (L-T4) enantiomer normalized, and basal and stimulated TSH decreased significantly without complete suppression. After 8 years off D-T4, at 20 years of age, clinical status was normal despite persisting high TH levels and inappropriate TSH. Evolution of serum markers of TH action and echocardiography measurements followed up from 15 months to 20 years of age either in basal condition or on triiodothyronine (T3), as well as the sequential determination of bone mineral density suggest differences in the tissue responses to T3: normal in bone with a high remodelling rate, heterogeneity for various hepatic markers, and decreased at heart level. No mutations were found in the coding sequence of TRβ1, TRβ2, TRα1, RXRγ, SMRT, NCoR1, and NCoA1. In this patient the putative long-term effects of the persisting high bone resorption are unknown

Iron and energy metabolic interactions in Treg-mediated immune regulation

Immunometabolism, the study of how metabolic processes influence immune cell function, has emerged as a critical field in understanding the regulation of immune tolerance and the pathological mechanisms underlying autoimmune diseases. Intracellular metabolic pathways not only provide the necessary energy for immune cell survival and activity but also shape the differentiation, phenotype, proliferation, and effector functions of immune cells. This is particularly evident in CD4+ Foxp3+ regulatory T cells (Treg), which are pivotal for maintaining immune homeostasis and preventing autoimmune reactions. Strong experimental evidence highlights the profound impact of metabolism on Treg. Their anti-inflammatory function and ability to suppress excessive immune responses depend on the integration of metabolic cues with their transcriptional and signaling networks. Iron metabolism and mitochondrial dynamics are among the key factors influencing Treg function. This review focuses on how iron and mitochondrial metabolism shape Treg biology and function