Protective effect of miR378* on doxorubicin‐induced cardiomyocyte injury via calumenin

Abstract

Doxorubicin (Dox) is a highly effective antitumor antibiotic, however myocardial toxicity severely limits its use clinically. The pathogenesis of doxorubicin‐induced cardiomyopathy is unclear. In Dox cardiomyopathy mice, there is a decline in cardiac function, a change in myocardial pathology and a reduction in miR378* expression. Expression changes in calumenin, an endoplasmic reticulum stress (ERS) chaperone protein and pathway factor, as well as apoptosis, were observed in cardiomyocytes after doxorubicin‐induced injury. However, miR378* increased calumenin expression, eased ERS, and reduced cardiomyocyte apoptosis, while, silencing miR378* reduced calumenin expression, aggravated ERS, and increased cardiomyocyte apoptosis. The above results indicate that miR378* alleviates ERS and inhibits the activation of the ERS‐mediated apoptosis signaling pathway in cardiomyocytes via regulating calumenin expression, thereby reducing cardiomyocyte apoptosis after doxorubicin‐induced injury. Increasing miR378* expression may be a new way to improve cardiac function and quality of life in patients with Dox cardiomyopathy.

Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway

“…Some studies have reported that ERS and autophagy play a role in the internal regulatory mechanism, Chen et al ( 31 ) reported that isodunnianol reduced myocardial damage caused by doxorubicin by activating protective autophagy, whereas Fu et al ( 32 ) reported that chemical endoplasmic reticulum chaperone molecules can alleviate Dox-induced cardiac dysfunction. miR378 alleviates ERS and inhibits activation of the ERS-mediated apoptosis signaling pathway in cardiomyocytes via regulating calumenin expression, thereby reducing cardiomyocyte apoptosis after doxorubicin-induced injury ( 33 ). Another study reported that doxorubicin blocks autophagic flux in cardiomyocytes by impairing lysosome acidification and lysosomal function.…”

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

“…CALU, a calcium-binding protein localized in the endoplasmic reticulum (ER), is mainly involved in such ER functions as protein folding and sorting. Besides, CALU has recently been shown to influence cell mobility, migration, invasion, and metastasis during particular events, such as tumorigenesis, wound healing, immune response, and coagulation [ 16 , 17 , 18 , 19 , 20 , 21 ]. Several studies have explored the relationship between CALU expression and survival and yielded relatively consistent results.…”

S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study

“…Calumenin was described to be secreted in the surrounding medium [ 9 ]. It has been widely evaluated in various cancers by influencing tumorigenesis and therapeutic response [ 10 ]. Increased expression of calumenin was associated with poorer outcome in gliomas [ 11 ].…”