hnRNP-A1 binds to the IRES of MELOE-1 antigen to promote its translation in stressed melanoma cells. Academic Article uri icon

Overview

abstract

  • The major challenge in antigen-specific immunotherapy of cancer is to select the most relevant tumor antigens to target. To this aim, understanding their mode of expression by tumor cells is critical. We previously identified a melanoma-specific antigen, melanoma-overexpressed antigen 1 (MELOE-1)-coded for by a long noncoding RNA-whose internal ribosomal entry sequence (IRES)-dependent translation is restricted to tumor cells. This restricted expression is associated with the presence of a broad-specific T-cell repertoire that is involved in tumor immunosurveillance in melanoma patients. In the present work, we explored the translation control of MELOE-1 and provide evidence that heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) binds to the MELOE-1 IRES and acts as an IRES trans-activating factor (ITAF) to promote the translation of MELOE-1 in melanoma cells. In addition, we showed that endoplasmic reticulum (ER) stress induced by thapsigargin, which promotes hnRNP-A1 cytoplasmic translocation, enhances MELOE-1 translation and recognition of melanoma cells by a MELOE-1-specific T-cell clone. These findings suggest that pharmacological stimulation of stress pathways may enhance the efficacy of immunotherapies targeting stress-induced tumor antigens such as MELOE-1.

authors

  • Charpentier, Maud
  • Dupré, Emilie
  • Fortun, Agnès
  • Briand, Floriane
  • Maillasson, Mike
  • Com, Emmanuelle
  • Pineau, Charles
  • Labarrière, Nathalie
  • Rabu, Catherine
  • Lang, François

publication date

  • August 21, 2021

Research

keywords

  • Antigens, Neoplasm
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Internal Ribosome Entry Sites
  • Melanoma
  • Neoplasm Proteins
  • Protein Biosynthesis

Identity

Digital Object Identifier (DOI)

  • 10.1002/1878-0261.13088

PubMed ID

  • 34418284