Key result
Nucleolin protects against doxorubicin-induced cardiac injury and dysfunction by upregulating microRNA-21.
Why the study?
The role of nucleolin in doxorubicin-induced cardiotoxicity and its underlying mechanisms were not fully understood.
Does nucleolin overexpression protect against doxorubicin-induced cardiotoxicity in preclinical models?
Does nucleolin overexpression protect against doxorubicin-induced cardiotoxicity in preclinical models?
Nucleolin protects against doxorubicin-induced cardiotoxicity via upregulation of miRNA-21, identifying a potential novel therapeutic target.
May identify nucleolin as a therapeutic target for doxorubicin cardiotoxicity; leaves open translation to clinical settings.
Nucleolin is a multifunctional protein and participates in many important biological processes. Our previous study found that nucleolin protects the heart against myocardial ischemia-reperfusion injury. In this study, we aimed to investigate the role of nucleolin in doxorubicin (DOX)-induced cardiotoxicity. The expression pattern of nucleolin in hearts subjected to DOX injury was investigated, and we found that administration of DOX induced nucleolin expression significantly in vivo and in vitro. Gene transfection and RNA interference approaches were used in cardiomyocytes to investigate the function of nucleolin. Nucleolin overexpression protects cardiomyocytes against DOX-induced injury. Nucleolin-ablated cardiomyocytes become susceptible to the injury induced by DOX. The hearts of cardiac-myocyte-specific nucleolin transgenic mice are more resistant to DOX injury. Furthermore, nucleolin upregulates microRNA(miRNA)-21 expression in vivo and in vitro, and the miRNA-21 inhibitor negates the protective effect of nucleolin against injury induced by DOX. These results have demonstrated that nucleolin is involved in the regulation of DOX-induced cardiac injury and dysfunction via the regulation of miRNA-21 expression, and may be a novel therapeutic target for DOX-induced cardiotoxicity.
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Sun et al. (2018) studied Doxorubicin-induced cardiotoxicity. Nucleolin overexpression vs. Nucleolin ablation or wild-type was evaluated on Doxorubicin-induced cardiac injury and dysfunction. Nucleolin protects against doxorubicin-induced cardiac injury and dysfunction by upregulating microRNA-21 expression in vivo and in vitro.
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