Fig. 6.
Exosomal miR-22-3p derived from failing cardiomyocytes suppresses ferroptosis of tumor cells. a qRT-PCR analysis on the expression of miR-22-3p in sham-Myo (adult ventricular cardiomyocytes harvested from mice subjected to sham operation), MI-Myo (adult ventricular cardiomyocytes harvested from mice subjected to MI) and exosomes from sham-Myo (Myo-EXOSham), exosomes from MI-Myo (Myo-EXOMI) (N = 3/group); b, c LLC cells were co-cultured with Myo-EXOSham or Myo-EXOMI (1 μg/mL) in the presence of erastin for 24 h. b Cell proliferation was assayed using an EdU staining kit (Bar: 40 μm) (N = 10 from 3 independent experiments); c Cell invasion was detected by transwell cell invasion assay (Bar: 100 μm) (N = 10 from 3 independent experiments); d, e LLC cells were treated with sham/MI exosomes (1 μg/mL) in the presence of erastin for 24 h after transfection with AMO-22-3p for 24 h. d Analysis of lipid-ROS accumulation using C11 BODIPY 581/591 fluorescence staining (Bar: 40 μm), Red, non-oxidized form of C11-BODIPY; Green, oxidized form of C11-BODIPY. Each data point represents the ratio of oxidized C11 to non-oxidized C11 signal (N = 8 from 3 independent experiments); e Representative images and quantitative results of LLC cancer cell colonies (N = 3 independent experiments); f Schematic depiction of in vivo experimental protocols for xenograft tumor induced by LLC cell transplantation in MI C57BL/6 mice with or without inhibition of cardiomyocyte specific miR-22-3p by its sponge carried by AAV9 with cTnT promoter; g Representative images of echocardiograph and statistical data on EF% and FS% (N = 7–8/group); h–j Representative images of tumors and the statistical analyses of on (i) tumor volumes and (j) tumor weights (N = 7–8/group); k H&E staining of subcutaneous xenograft tissues (Bar: 20 μm); l qRT-PCR analysis of the expression of miR-22-3p in heart tissues, plasma exosomes and tumor tissues (N = 3/group). Data are expressed as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001