PSMD3 siRNA

PSMD3 siRNA is an experimental small interfering RNA (siRNA) therapeutic designed to silence the expression of the PSMD3 gene, which encodes the 26S proteasome non-ATPase subunit 3 (also known as Rpn3). PSMD3 is a critical scaffold subunit of the 19S regulatory particle (RP) of the 26S proteasome, responsible for proteasome assembly. In multiple myeloma (MM), PSMD3 is frequently overexpressed and associated with poor survival. siRNA-mediated knockdown of PSMD3 disrupts the assembly of the 26S proteasome, leading to the accumulation of polyubiquitinated proteins, activation of the endoplasmic reticulum (ER) stress response, and mitochondrial dysfunction. This cascade ultimately triggers apoptosis and immunogenic cell death (ICD) via the cGAS-STING pathway. Preclinical studies suggest that targeting PSMD3 can overcome resistance to conventional proteasome inhibitors (PIs) such as bortezomib and carfilzomib, providing a potential therapeutic strategy for PI-resistant multiple myeloma.

Other names

PSMD3-siRNAPSMD-3-siRNAPSMD 3-siRNAsiPSMD3siPSMD-3siPSMD 3siRNA-mediated PSMD3 knockdown