Mutant IDH1-mediated modulation of SOX9 and CDKN1C expression regulated chondrosarcoma tumor progression, and DS-1001b upregulated the expression of these genes via a common mechanism involving the demethylation of H3K9me3.
Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-β signalling are mutually inhibitory in chondrosarcoma cells.
The present study demonstrated that T cell factor 1 (TCF-1) protein, a component of the canonical Wnt/β-catenin signaling pathway, can regulate the expression of runt-related transcription factor 2 (runx2) gene and Sry-related HMG box 9 (sox9) gene, which may participate in the differentiation of chondrosarcoma.
Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells.
Expression of SOX9 in human chondrosarcomas is novel and suggests that chondrosarcomas originate from a multipotent stem cell committed to differentiation along the chondrogenic pathway.