PAPSS1 siRNA

**PAPSS1 siRNA** is a small interfering RNA therapeutic designed to silence the expression of the PAPSS1 (3'-phosphoadenosine 5'-phosphosulfate synthase 1) gene. PAPSS1 is a dual-function enzyme that synthesizes PAPS, the biologically active form of sulfate used in sulfonation reactions. This siRNA was identified through a genome-wide siRNA screen as a sensitizing agent for cancer chemotherapy. When PAPSS1 is knocked down using siRNA, cancer cells become significantly more sensitive to DNA-damaging agents, particularly cisplatin and other platinum-based chemotherapies. The mechanism involves increasing DNA damage, inducing G1/S phase cell cycle arrest, promoting apoptosis, and reducing DNA repair capacity in cancer cells. PAPSS1 silencing has been shown to reduce clonogenicity of non-small cell lung cancer (NSCLC) cells by up to 98.7% when combined with low-dose cisplatin. The therapeutic effect extends to ovarian cancer and has been validated in multiple preclinical models including multi-cellular tumor spheroids, zebrafish, and rodent models. Notably, PAPSS1 knockdown sensitizes cancer cells to radiation, DNA crosslinkers (carboplatin, oxaliplatin, mitomycin C), and topoisomerase I inhibitors, but not topoisomerase II inhibitors. The sensitization is selective for cancer cells, as normal bronchial epithelial cells do not show increased sensitivity to cisplatin when PAPSS1 is inhibited. Research indicates the mechanism involves post-translational sulfation of proteins rather than sulfate bioavailability for amino acid synthesis, as yeast homolog deletion does not sensitize yeast to cisplatin.

Other names

PAPSS1-targeting siRNAPAPSS-1-targeting siRNAPAPSS 1-targeting siRNAsiPAPSS1siPAPSS-1siPAPSS 1