Heat shock cognate 71 kDa protein mRNA (HSPA8 mRNA)

HSPA8 mRNA encodes the Heat shock cognate 71 kDa protein (Hsc70), a constitutively expressed member of the Hsp70 chaperone family (UniProt P11142). Unlike inducible heat shock proteins, HSPA8 is essential for cellular homeostasis, performing critical roles in protein folding, the disassembly of clathrin-coated vesicles, and chaperone-mediated autophagy (CMA) (PubMed: 11557750, 25663481). In CMA, the HSPA8 protein recognizes specific motifs in substrate proteins and facilitates their delivery to lysosomes for degradation, a pathway often hijacked in cancer cells to support survival and proliferation (PubMed: 30104694). Consequently, HSPA8 mRNA is an emerging target for knockdown strategies using RNA interference or antisense oligonucleotides to induce proteotoxic stress in malignant cells. In the context of disease, HSPA8 mRNA is frequently upregulated in various malignancies, including breast and lung cancers, where it contributes to tumor progression and resistance to therapy (PubMed: 30104694). In autoimmune conditions like systemic lupus erythematosus (SLE), the HSPA8 protein is involved in the processing and presentation of self-antigens; the therapeutic peptide P140 (Lupuzor) targets the HSPA8 protein to modulate this process and has reached Phase III clinical trials (PubMed: 26153141). While most current clinical efforts focus on the protein product, HSPA8 mRNA remains a primary target for experimental RNA-based therapeutics aimed at depleting Hsc70 levels. However, because HSPA8 is a housekeeping gene with essential functions, therapeutic strategies must carefully manage the risk of systemic toxicity and the impairment of normal cellular proteostasis.

Other names

HSC70 mRNAHSC71 mRNAHSPA8 transcriptHeat shock 70kDa protein 8 mRNANAMP mRNA

RNA interference and antisense-mediated degradation or translational inhibition