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Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage. | LitMetric

AI Article Synopsis

  • Myocardial damage is a serious complication of multiple myeloma (MM) impacting patient treatment and quality of life, and exosomal circular RNAs (exo-circRNAs) could be key factors in understanding this relationship.
  • The study involved six MM patients and five healthy controls to investigate how exo-circRNAs are expressed and their potential role in myocardial damage linked to MM, utilizing various bioinformatics and laboratory techniques.
  • Results indicated that a specific circRNA, circ-G042080, is associated with MM and myocardial damage, suggesting it might influence this damage through a mechanism involving miRNA and TLR4 pathways, leading to abnormal cell autophagy.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201884PMC
http://dx.doi.org/10.1186/s12935-021-02011-wDOI Listing

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