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

Manya Yu1, Lin Ji2, Sumei Li1

  • 1Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, 250014, China.

Experimental Cell Research
|June 1, 2022
PubMed

Insights

Multiple myeloma exosomes harm heart cells by promoting apoptosis and reducing viability. This involves circ-CACNG2, which impacts miR-197-3p and caspase3, indicating a new mechanism for cardiac complications in multiple myeloma (MM).

Area of Science:

  • Cardiology
  • Oncology
  • Molecular Biology

Background:

  • Multiple myeloma (MM) exosomes contribute to complications like bone lesions and renal failure.
  • The specific mechanisms by which MM exosomes affect cardiac function remain unclear.
  • Understanding exosome-mediated cardiac damage is crucial for MM patient care.

Purpose of the Study:

  • To investigate the impact of MM exosomes on cardiomyocyte viability, cell cycle, oxidative stress, and apoptosis.
  • To elucidate the role of circular RNA CACNG2 (circ-CACNG2) in MM-induced cardiac effects.
  • To identify the molecular pathways involved in MM exosome-mediated cardiomyocyte dysfunction.

Main Methods:

  • Co-culture of H9C2 cardiomyocytes with U266 MM cell line exosomes (U266-exo).
  • Analysis of circ-CACNG2 levels in MM patient serum exosomes.
  • In vitro experiments including viability assays, apoptosis assays, RIPA, pull-down assays, dual-luciferase reporter assays, and RNA FISH.
  • Rescue experiments to validate the molecular mechanism.

Main Results:

  • U266-exo significantly inhibited H9C2 cell viability and promoted apoptosis.
  • MM patient serum exosomes showed elevated levels of circ-CACNG2.
  • circ-CACNG2 was identified as an independent prognostic and diagnostic indicator for MM-related cardiac complications.
  • circ-CACNG2 directly binds to miR-197-3p and caspase3, regulating apoptosis via the circ-CACNG2/miR-197-3p/caspase3 axis.

Conclusions:

  • MM exosomes impair cardiomyocyte viability and induce apoptosis.
  • The circ-CACNG2/miR-197-3p/caspase3 pathway is a key mechanism in MM-exosome-induced cardiac complications.
  • circ-CACNG2 serves as a potential biomarker for predicting and diagnosing cardiac issues in multiple myeloma patients.
Keywords:
ApoptosisCardiac complicationCircular RNAExosomeMultiple myeloma

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