| First Author | Zhang WC | Year | 2019 |
| Journal | Cell Cycle | Volume | 18 |
| Issue | 23 | Pages | 3263-3274 |
| PubMed ID | 31627713 | Mgi Jnum | J:298394 |
| Mgi Id | MGI:6480069 | Doi | 10.1080/15384101.2019.1673618 |
| Citation | Zhang WC, et al. (2019) miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITCH. Cell Cycle 18(23):3263-3274 |
| abstractText | Objective: To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury.Methods: The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITCH, TNF-alpha and IL-6 were measured by qRT-PCR. Protein levels of ITCH, NF-kappaB, TNF-alpha and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITCH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox.Results: Dox reduced HL-1 cell viability and activated NF-kappaB pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITCH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITCH. Besides, ITCH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITCH expression, increased TNF-alpha and IL-6 level, and promoted NF-kappaB expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITCH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy.Conclusion: miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITCH/NF-kappaB pathway. |
