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Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage
Runjie Sun1, Wei Liu2, Yangang Zhao3
1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, 250014, China.
Introduction:
Myocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage.
Methods:
Six MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles.
Results:
Bioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy.
Conclusion:
Abnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.
Insights
Exosomal circular RNAs (exo-circRNAs) are linked to myocardial damage in multiple myeloma (MM). Circ-G042080 may serve as a diagnostic marker and therapeutic target for MM-related heart conditions.
Area of Science:
- Oncology
- Cardiology
- Molecular Biology
- Exosome Biology
Background:
- Multiple myeloma (MM) frequently causes incurable myocardial damage, impacting patient outcomes and quality of life.
- Exosomal circular RNAs (exo-circRNAs) are implicated in cancer development, but their role in MM-related myocardial damage is unknown.
- Understanding exo-circRNAs is crucial for developing new diagnostic and therapeutic strategies for MM patients.
Purpose of the Study:
- To investigate the correlation between exo-circRNAs and multiple myeloma (MM).
- To explore the potential role and mechanism of exo-circRNAs in MM-related myocardial damage.
- To identify potential diagnostic markers and therapeutic targets for MM-associated cardiac complications.
Main Methods:
- High-throughput sequencing and qRT-PCR were used to profile exo-circRNAs in MM patients and healthy controls.
- Bioinformatics analyses (GO, KEGG, miRanda, TargetScan, Metascape) were performed to predict functions and pathways.
- In vitro experiments using H9C2 cells treated with MM exosomes assessed cell proliferation, autophagy, and molecular mechanisms (TLR4 axis).
Main Results:
- Upregulated circRNAs were identified as potential drivers of MM-related myocardial damage.
- Circ-G042080 was significantly upregulated in MM patient serum exosomes and positively correlated with MM severity and myocardial damage.
- The circ-G042080/hsa-miR-4268/TLR4 axis was implicated in MM-related myocardial damage and abnormal autophagy in H9C2 cells.
Conclusions:
- Abnormal serum exo-circRNA expression is associated with multiple myeloma-related myocardial damage.
- Exo-circRNAs, particularly circ-G042080, show promise as novel diagnostic biomarkers for MM-related myocardial damage.
- The identified exo-circRNA pathways represent potential therapeutic targets for mitigating MM-associated cardiac complications.
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