Related Experiment Video
Updated: Jun 17, 2025
Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity
Xin Chen1, Liwen Wang1, Qian Cheng1
1Department of Hematology, the Third Xiangya Hospital of Central South University, Changsha 412000, China.
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.
Insights
Multiple myeloma cells transfer microRNAs (miRNAs) via exosomes to suppress monocyte antiviral defenses. Targeting these specific miRNAs offers a new therapeutic strategy for preventing DNA virus infections in multiple myeloma patients.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Multiple myeloma (MM) patients exhibit increased susceptibility to DNA virus infections.
- Monocyte dysfunction is implicated in MM-related infectious complications, but the underlying mechanisms are unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which multiple myeloma cells impair monocyte antiviral immunity.
- To identify specific microRNAs (miRNAs) involved in this immune suppression.
- To evaluate a potential therapeutic strategy targeting these miRNAs.
Main Methods:
- Analysis of microRNAs (miRNAs) within exosomes derived from multiple myeloma (MM) patient bone marrow.
- In vitro and in vivo studies using MM cell lines and MM-bearing mouse models (C57BL/KaLwRijHsd).
- Silencing of specific miRNAs using antagomiRs to assess impact on viral replication and innate immune response.
Main Results:
- Multiple myeloma (MM) cells transfer microRNAs (miRNAs) to monocytes/macrophages via exosomes, inhibiting innate antiviral responses.
- Five specific miRNAs enriched in MM-derived exosomes were identified as negative regulators of the cGAS-STING antiviral pathway.
- AntagomiR-mediated silencing of these miRNAs in a mouse model significantly reduced DNA virus replication.
Conclusions:
- Multiple myeloma (MM) cells actively suppress host innate antiviral immunity through exosomal miRNA transfer.
- Targeting aberrant miRNA expression in MM patients presents a promising therapeutic approach to enhance antiviral defense.
- A predictive model integrating miRNA scores and clinical factors can assess DNA viral infection susceptibility in MM patients.
