Fig. 3: Sotorasib-mediated upregulation of NEU1 contributes to cardiomyocyte apoptosis.
From: Sotorasib-impaired degradation of NEU1 contributes to cardiac injury by inhibiting AKT signaling
A Proteomic analysis of CCC-HEH-2 cell samples from control and sotorasib groups (n = 3). Volcano Plot. B CCC-HEH-2 cells transfected with NC or MTP18, HMOX1, NEU1, REEP1, and AKT1 siRNA were treated with sotorasib for 48 h. Expression levels of c-PARP protein in CCC-HEH-2 cells (n = 3). C CCC-HEH-2 were exposed to different concentrations of 0, 10, 15, or 20 μM sotorasib for 48 h. c-PARP and NEU1 expression levels in CCC-HEH-2 cells (n = 3). Male C57BL/6J mice were treated with 0.5% CMC-Na or sotorasib (300 mg/kg/d or 600 mg/kg/d) by gavage for 28 days. D Representative image of NEU1 IHC in heart tissue (n = 3). Scale bar: 50 μm. E NEU1 protein expression levels in mouse tissues (n = 3). CCC-HEH-2 cells transfected with NC, NEU1#1 or NEU1#2 knockdown were treated with sotorasib for 48 h. F c-PARP and NEU1 expression levels in CCC-HEH-2 cells (n = 3). G Survival fraction and representative pictures of CCC-HEH-2 cells (n = 3). Scale bar: 10 μm. H CCC-HEH-2 cells were transfected with NEU1-HA plasmid overexpressing NEU1 at concentrations of 0, 0.5, 0.75 and 1.0 μg, respectively, for 48 h. HA and c-PARP expression levels in CCC-HEH-2 cells (n = 3). I CCC-HEH-2 cells were transfected with 0.5 μg PCDH or NEU1-HA plasmid after sotorasib treatment for 36 h. HA and c-PARP expression levels in CCC-HEH-2 cells (n = 3). Data expressed as mean ± SD, ***, p < 0.0001, **, p < 0.01, *, p < 0.05 (vs. Vehicle), #, p < 0.05 (vs. NC+sotorasib), &, p < 0.05 (vs. siNEU1#2 or NEU1-HA), ns, no significance.
