Dickkopf-related protein 1 mRNA (DKK1 mRNA) (DKK1 mRNA)

Dickkopf-related protein 1 (DKK1) mRNA encodes a secreted glycoprotein that functions as a potent antagonist of the canonical Wnt/beta-catenin signaling pathway (UniProt O94907). By binding to the LRP5/6 co-receptors and Kremen proteins, the DKK1 protein induces the internalization of the LRP complex, thereby preventing Wnt ligands from activating the pathway and downstream gene expression (NCBI Gene ID: 22943). In various pathological contexts, particularly in multiple myeloma and several solid tumors, DKK1 mRNA is frequently overexpressed, which contributes to tumor-induced osteolytic bone disease and immune suppression within the tumor microenvironment (PubMed: 30135149). Therapeutic targeting of DKK1 mRNA using small interfering RNAs (siRNAs) or antisense oligonucleotides (ASOs) aims to silence the expression of the DKK1 protein at the pre-translational level (PubMed: 22431585). This approach is intended to restore Wnt signaling activity, promote osteoblast differentiation in bone-wasting diseases, and enhance anti-tumor immune responses. While protein-targeting antibodies like DKN-01 are currently in clinical development, mRNA-directed therapies represent an emerging strategy to achieve more comprehensive or tissue-specific inhibition of DKK1 activity.

Other names

Dickkopf-1 mRNADKK-1 mRNASK mRNADickkopf-related protein 1 transcripthDkk-1 mRNA

RNA interference (siRNA) or RNase H-mediated cleavage (ASO) of the DKK1 transcript to prevent the translation of the Dickkopf-related protein 1, thereby restoring canonical Wnt signaling.