hnRNP-A1 binds to the IRES of MELOE-1 antigen to promote MELOE-1 translation in stressed melanoma cells.
Mol Oncol
; 16(3): 594-606, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34418284
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
/
Sitios Internos de Entrada al Ribosoma
/
Ribonucleoproteína Nuclear Heterogénea A1
/
Melanoma
/
Antígenos de Neoplasias
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Francia