Heat shock protein family A (Hsp70) member 5 mRNA (HSPA5 mRNA) (HSPA5 mRNA)

HSPA5 mRNA encodes the Heat shock protein family A (Hsp70) member 5, widely known as GRP78 or BiP, which is a master chaperone located in the lumen of the endoplasmic reticulum (ER) (UniProt P11021; NCBI Gene 3309). This mRNA is a primary target of the unfolded protein response (UPR), a signaling pathway activated by ER stress to increase the cell's folding capacity and ensure protein quality control (Ibrahim et al., 2019, Life Sciences). In many pathological conditions, particularly aggressive cancers, HSPA5 mRNA is significantly overexpressed, providing a survival advantage to tumor cells under hypoxic and nutrient-deprived conditions (Wang et al., 2009, Free Radic Biol Med). Targeting HSPA5 mRNA with RNA-based therapeutics, such as antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), aims to silence the production of GRP78, thereby sensitizing cancer cells to chemotherapy and inducing apoptosis (Lee, 2005, Methods). Beyond oncology, HSPA5 mRNA levels are modulated in neurodegenerative diseases and viral infections, where the protein product acts as a co-receptor for viral entry, including for SARS-CoV-2 (UniProt P11021). Consequently, HSPA5 mRNA represents a high-value therapeutic target for restoring cellular homeostasis or selectively eliminating stressed cells in various diseases.

Other names

GRP78 mRNABiP mRNA78 kDa glucose-regulated protein mRNAEndoplasmic reticulum lumenal Ca(2+)-binding protein grp78 mRNA

RNA interference (siRNA) or RNase H-mediated cleavage (antisense oligonucleotides) leading to reduced translation of the GRP78 protein (Lee, 2005; Wang et al., 2009).