1. Academic Validation
  2. Exosomal circ-CACNG2 promotes cardiomyocyte apoptosis in multiple myeloma via modulating miR-197-3p/caspase3 axis

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

  • Exp Cell Res. 2022 Aug 15;417(2):113229. doi: 10.1016/j.yexcr.2022.113229.
Manya Yu 1 Lin Ji 2 Sumei Li 1 Yanyu Zhang 1 Xiaoqi Sun 1 Runjie Sun 1 Xiubao Chen 3 Yaqin Luo 4 Xing Cui 5
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan, 250014, China.
  • 2 Department of Neurology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250001, China.
  • 3 Department of Health Care, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, China.
  • 4 Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, China.
  • 5 Department of Oncology and Hematology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250001, China. Electronic address: cdz45@foxmail.com.
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.

Keywords

Apoptosis; Cardiac complication; Circular RNA; Exosome; Multiple myeloma.

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