RNA-seq of 8988t cells
About eighty percent of pancreatic cancers are prone to liver metastasis, even after surgical resection. However, the underlying molecular mechanisms that drive liver metastasis remain largely undefined, calling for the development of effective drugs. Here, a pancreatic cancer tissue-based SELEX technology was performed to identify aptamers that specifically bind pancreatic cancers with high liver metastatic potential. Subsequently, an aptamer-drug conjugate (ApDC) was developed that significantly suppressed pancreatic cancer liver metastasis in mouse models. The aptamer targets Serpine1 mRNA Binding Protein 1 (SERBP1), which is an mRNA-binding protein found to have elevated levels in various cancers. We discovered that SERBP1 binds and stabilizes CEBPB mRNA which encodes the CCAAT enhancer-binding protein beta (CEBPB), a b-Zip transcription factor that mediates TNF signaling activated and upregulates the expression of aspartate beta-hydroxylase (ASPH), collectively promoting the progression of liver metastasis. In summary, this research establishes a novel SERBP1-CEBPB-ASPH axis as decisive in driving pancreatic liver metastasis and establishes SERBP1-targeted aptamer as a promising predictor of metastatic risk and potential tool for targeted therapy.