Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity.
Biochim Biophys Acta Mol Basis Dis
; 1870(8): 167457, 2024 Dec.
Article
en En
| MEDLINE
| ID: mdl-39134287
ABSTRACT
DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Exosomas
/
Inmunidad Innata
/
Proteínas de la Membrana
/
Ratones Endogámicos C57BL
/
Mieloma Múltiple
/
Nucleotidiltransferasas
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
China