The clinical significance of thyroid hormone-responsive in thyroid carcinoma and its potential regulatory pathway.

The study aimed to evaluate the clinical significance of thyroid hormone-responsive (THRSP) and explore its relevant pathways in thyroid carcinoma (THCA). The gene expression data of THRSP were obtained and the prognostic significance of THRSP in THCA was analyzed through various bioinformatics databases. Then, the factors influencing THRSP mRNA expression were explored, and the function of THRSP in predicting the lymph node metastasis (LNM) stage was determined. We further performed the enrichment analysis and constructed a protein-protein interaction (PPI) network to examine potential regulatory pathways associated with THRSP. THRSP gene expression was significantly increased in THCA compared with the normal tissues. High THRSP mRNA expression had a favorable overall survival (OS) in THCA patients (P < .05). Additionally, the mRNA expression of THRSP was related to stage, histological subtype, and methylation among THCA patients (all P < .05). Besides, THRSP served as a potent predictor in discriminating the LNM stage of thyroid cancer patients. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) on THRSP-associated genes, THRSP was positively related to metabolic pathways. The upregulation of THRSP predicted a good OS in THCA patients. Furthermore, THRSP might inhibit THCA progression through positive regulation of metabolism-associated pathways.

FIM-A, a phosphorus-containing sirolimus, inhibits the angiogenesis and proliferation of osteosarcomas.

The mTOR pathway is a central control of cell growth, proliferation, metabolism, and survival, and is deregulated in most cancers. Cancer cells are addicted to increased activity of mTOR kinase-mediated signaling pathways, leading to numerous inhibitors of mTOR signaling in preclinic and clinical trials for cancer therapy. Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling, inhibits cancer cell growth in vitro. Here we report that FIM-A reduces the angiogenesis and proliferation of osteosarcoma both in vitro and in vivo. In cultured osteosarcoma cell lines, FIM-A inhibited cell proliferation and arrested cells in the G1 phase of the cell cycle, accompanied with reduction of VEGF and HIF-1alpha. With in vivo mouse osteosarcoma xenografts, FIM-A treatment resulted in the inhibition of mTORC1 signaling as demonstrated by the decreased phosphorylation of p70S6K1 and 4E-BP1. Consistent with this finding, FIM-A significantly decreased the average tumor volume, nuclei staining of PCNA, and the number of intratumoral microvessels. Our data demonstrated that targeting mTORC1 by FIM-A inhibited the growth of osteosarcoma in vitro and in vivo, providing the basis for further development of FIM-A as a therapy for osteosarcoma patients.