BAG family molecular chaperone regulator 3 (BAG3) mRNA (BAG3 mRNA)

BAG family molecular chaperone regulator 3 (BAG3) mRNA encodes a versatile co-chaperone protein that plays a pivotal role in maintaining cellular protein homeostasis (proteostasis) and regulating cell survival (UniProt: O95817). The BAG3 protein acts as a bridge between the molecular chaperone Hsp70 and the machinery for macroautophagy, specifically through the chaperone-assisted selective autophagy (CASA) pathway (Kohnke et al., 2017). In various malignancies, including pancreatic cancer and glioblastoma, BAG3 mRNA is significantly upregulated, where it functions to inhibit apoptosis and promote tumor cell resistance to therapy (Rosati et al., 2011). Consequently, BAG3 mRNA has emerged as a therapeutic target for RNA-based interventions, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), designed to downregulate its expression and sensitize cancer cells to treatment (Rapino et al., 2014). However, BAG3 is also essential for the structural integrity and function of cardiomyocytes and skeletal muscle; mutations in the BAG3 gene are a known cause of dilated cardiomyopathy and myofibrillar myopathy (Kohnke et al., 2017). Therefore, therapeutic strategies targeting BAG3 mRNA must carefully balance the need for potent downregulation in diseased tissues with the risk of inducing cardiotoxicity or muscular dysfunction.

Other names

BCL2-associated athanogene 3 mRNABAG-3 mRNABCL2-binding athanogene 3 mRNABIS mRNACAIR-1 mRNA

RNase H-mediated mRNA degradation or RNA interference (RNAi) to reduce BAG3 protein expression