biostudies-literature00560Sun RKey Technology Research and Development Program of ShandongNational Natural Science Foundation of ChinaTaishan Scholar Foundation of Shandong Province311https://www.ebi.ac.uk/biostudies/studies/S-EPMC8201884biostudies-literatureUnknown21(1)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Cancer cell internationalExosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage.PMC8201884No.81774080No.2019GSF108162tsqn201812145Sun RZhang YCui XChen HSun XWang ZZhao YLiu W56falseExosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.2021-01-01T00:00:00Z2021 Jun2024-02-15T08:52:17.922Z2022-02-10T14:55:28.162ZS-EPMC82018843412060610.1186/s12935-021-02011-w