SOX12 cooperates with YBX1 to facilitate papillary thyroid cancer metastasis by transcriptionally upregulating LDHA

we analyzed single-cell RNA-seq and Bulk RNA-seq datasets and found that SOX12 was obviously upregulated in PTC, indicating poor prognosis in PTC patients. Overexpression of SOX12 promoted the metastasis of PTC cells, while downregulation of SOX12 impaired the aggressiveness of PTC. Integration of RNA-seq, CUT&Tag, and immunoprecipitation mass spectrometry (IP-MS) data revealed that SOX12 directly induces YBX1 expression and recruits it to the LDHA promoter, leading to an activated TGF-beta signaling pathway. Meanwhile, knockdown of LDHA rescued SOX12/YBX1- mediated activation of TGF-beta signaling pathway as well as migration and invasion of PTC cells. We also demonstrated that SOX12 expression is positively correlated with YBX1 and LDHA expression levels in clinical PTC samples. These results provide a critical link between the SOX12-YBX1-LDHA signaling axis and metastasis and suggest that targeting this signaling node may represent a valuable alternative strategy to combat PTC metastasis.