Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response.
Wojciech BarczakSimon Mark CarrGeng LiuShonagh MunroAnnalisa NicastriLian Ni LeeClaire HutchingsNicola TernettePaul KlenermanAlexander KanapinAnastasia SamsonovaNicholas B La ThanguePublished in: Nature communications (2023)
Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.
Keyphrases
- long non coding rna
- amino acid
- dendritic cells
- poor prognosis
- genome wide
- gene expression
- dna methylation
- induced apoptosis
- long noncoding rna
- immune response
- drug delivery
- protein protein
- nitric oxide
- sars cov
- papillary thyroid
- anti inflammatory
- cell cycle arrest
- binding protein
- squamous cell carcinoma
- peripheral blood
- regulatory t cells
- oxidative stress
- small molecule
- cancer therapy
- bioinformatics analysis
- signaling pathway
- endoplasmic reticulum stress
- cell death
- childhood cancer
- lymph node metastasis