Bcl-2-like protein 12 (BCL2L12) mRNA (BCL2L12 mRNA)

Bcl-2-like protein 12 (BCL2L12) is a member of the BCL2 family that acts as a potent inhibitor of apoptosis by neutralizing post-mitochondrial caspase activation and inhibiting p53 activity (UniProt Q9HB09; Stegh et al., 2007). Unlike other BCL2 family members, BCL2L12 primarily functions downstream of the mitochondria to block effector caspases like caspase-3 and caspase-7 (Stegh et al., 2008). It is significantly overexpressed in glioblastoma multiforme (GBM), where it contributes to tumor cell survival and resistance to therapy (Stegh et al., 2007). Because BCL2L12 lacks a traditional small-molecule binding pocket, therapeutic efforts have focused on its messenger RNA (mRNA) using RNA interference (RNAi) strategies. NU-0129 is a clinical-stage drug consisting of spherical nucleic acids (SNAs) that deliver siRNA targeting BCL2L12 mRNA across the blood-brain barrier (Kumthekar et al., 2021). By knocking down BCL2L12 mRNA, these therapies aim to restore the apoptotic machinery in cancer cells and enhance the efficacy of standard treatments. This target represents a novel approach in precision oncology for high-grade gliomas (Northwestern University, 2021).

Other names

Bcl2-L-12 mRNABCL2L12 transcriptBcl-2-like 12 mRNA

RNA interference (siRNA-mediated gene silencing)