THRA (Thyroid Hormone Receptor Alpha)

Highlights Mutation screening of TRα as a potential therapeutic target for thyroid carcinoma.Extraction and characterization of selective novel flavonoids from Myrica rubra.MTT analysis of quercetin, myricetin, and apigenin on CRISPR-KO TRα cell lines.Quercetin resulted most significantly in all in vitro and in silico parameters, despite myricetin and apigenin also showing unique patterns of cell growth arrest properties.GES (±) cell lines were verified using ddPCR, Sanger sequencing, and Western blotting as Post-CRISPR-Cas9 KO molecular screening. The online version contains supplementary material available at 10.1007/s13205-025-04543-8.

Our data reveal the significant association of THRA mutations potentially influencing cellular plasticity in a subset of patients with ATC.

As the most prominent one, compound 6c showed the highest anticancer activity against the MDA-MB-231 cell line and an IC50 value of 3.01 ± 0.45 µM, which was close to that of the positive control Doxorubicin (IC50 value of 3.10 ± 0.27 µM). It was also observed that compound 8e (IC50 = 3.92 ± 0.04 μM) exhibited superior activity against the T47D cell line, whereas compound 6f (IC50 = 2.10 ± 0.21 μM) demonstrated better activity against the MCF-7 cell line. In silico docking investigations of the representative ligands further explored the characteristic binding orientations on conserved interactions with residues like LysA:55, ValA:60, ThrA:11, GluA:14, ProA:57, AlaA:15, SerA:51, and GlyA:58 from 1U9E. The tested compounds' structure-activity relationships are in good agreement with molecular docking and DFT studies, which demonstrate that the primary cause of the high anticancer activity of 1,2,4-triazole hybrids is the presence of a lipophilic and heterocyclic substituent on the benzo[d]oxazole component.

Additionally, single-cell RNA sequencing revealed that THRB was primarily expressed in CD16+ monocytes within tumor tissues and was associated with a poor OS rate. Reduced THRB expression, but not THRA, was correlated with decreased OS in HCC patients.

P=N/A, N=350, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

This review examines the structural studies on TRs, primarily performed through X-ray crystallography, that have provided detailed insights into TR functions, including DNA recognition, ligand binding, and coregulator interactions. We also discuss how these findings have deepened our understanding of TR mechanisms and contributed to the interpretation of pathogenic mutations.

P=N/A, N=150, Recruiting, Istituto Auxologico Italiano

The predictive accuracy of the prognostic signature was further evaluated by the time-dependent ROC, with 1-, 2-, and 3-year AUCs of 0.86, 0.81, and 0.71, respectively. This study may provide new markers for individualized diagnosis and prognostic assessment of LUAD and potential targets for precision treatment.

Importantly, scRNA-seq analysis showed that TRα1-induced PAX8, via its transcription program, shifts the cell landscape of ATC toward a differentiated state. The present studies suggest that TRα1 is a newly identified regulator of thyroid differentiation and could be considered as a potential therapeutic target to improve the outcome of ATC patients.

High infiltration of anti-tumor immune cells in both tumors and margins results in good prognosis, while in patients with minimal infiltration in tumors in spite of high infiltration in margins results in poor prognosis. Targeted CD73 immune-checkpoint inhibition may improve clinical outcome.

The study reveals that WFDC2, TTLL12, THRA, and EPHB3 play crucial roles as UC-CRC critical genes and are positively correlated with the molecular transformation of UC to CRC. Taken together, these genes can be used as potential biomarkers and therapeutic targets for combating UC-induced human CRC.