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Exosomal circ-CACNG2 promotes cardiomyocyte apoptosis in multiple myeloma via modulating miR-197-3p/caspase3 axis. | LitMetric

AI Article Synopsis

  • Multiple myeloma (MM) exosomes impact cardiac complications by inhibiting cell viability and promoting apoptosis in heart cells (H9C2).
  • Some patients with MM had high levels of circ-CACNG2 in their serum exosomes, which was linked to cardiac complications and served as a potential diagnostic marker.
  • The study revealed that circ-CACNG2 affects the miR-197-3p/caspase3 pathway, suggesting a mechanism through which MM-exosomes contribute to heart cell damage.

Article Abstract

Multiple myeloma (MM) secreted exosomes are essential in MM-related complications such as osteolytic bone lesions and renal failure, but their role and underlying mechanism in cardiac complications has not yet been clarified. Here, we investigated the effects of U266 (a MM cell line) exosomes (U266-exo) on regulating the viability, cell cycle, oxidative stress and apoptosis of H9C2 cells and the role of circ-CACNG2 in these effects. We found that U266-exo coculture significantly inhibited viability and promoted apoptosis of H9C2 cells, and serum exosomes of MM patients harbored high level of circ-CACNG2. The clinical data analyses indicated that circ-CACNG2 was an independent prognostic and diagnostic indicator of MM-related cardiac complications. Also, in vitro experiments showed that circ-CACNG2 inhibited viability and promoted apoptosis of H9C2 cells. RIPA, pull-down assays, dual-luciferase reporter assays, and RNA FISH assays revealed that miR-197-3p could bind to circ-CACNG2 and caspase3 directly. Rescue experiments proved that circ-CACNG2 can increase the expression of caspase3 by binding to and decreasing the expression of miR-197-3p. In conclusion, MM-exosomes could inhibit cardiomyocyte viability and promote apoptosis partially through circ-CACNG2/miR-197-3p/caspase3 axis.

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Source
http://dx.doi.org/10.1016/j.yexcr.2022.113229DOI Listing

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