Prolyl 4-hydroxylase subunit beta mRNA (P4HB mRNA)

Prolyl 4-hydroxylase subunit beta (P4HB) mRNA encodes the beta subunit of prolyl 4-hydroxylase, which is functionally identical to the multifunctional enzyme protein disulfide-isomerase (PDI). PDI is a critical chaperone located in the lumen of the endoplasmic reticulum (ER), where it catalyzes the formation, breakage, and rearrangement of disulfide bonds to ensure proper folding of nascent proteins (UniProt P07237). In various malignancies, such as glioblastoma, hepatocellular carcinoma, and prostate cancer, P4HB mRNA is significantly upregulated to help tumor cells manage the high proteotoxic stress associated with rapid proliferation and hypoxia (PubMed: 28637125, PubMed: 30271493). Targeting P4HB at the mRNA level using RNA interference (RNAi) or antisense oligonucleotides (ASOs) is an emerging therapeutic strategy designed to deplete the cellular pool of PDI. This depletion triggers the unfolded protein response (UPR) and leads to terminal ER stress and apoptosis, particularly in cancer cells that have become dependent on high PDI levels for survival and chemoresistance (PubMed: 25100573). Beyond oncology, P4HB mRNA is also investigated in the context of neurodegenerative diseases and fibrotic conditions where protein misfolding and collagen assembly are central to disease progression.

Other names

Protein disulfide-isomerase mRNAPDI mRNAPDIA1 mRNAPHDB mRNAERBA2L mRNAPO4DB mRNAProlyl 4-hydroxylase beta polypeptide mRNA

RNA interference (RNAi) or RNase H-mediated degradation of the P4HB transcript to inhibit the translation of protein disulfide-isomerase (PDI), thereby disrupting protein folding and inducing endoplasmic reticulum stress-mediated apoptosis.