The miR-495-3p agomir prevented doxorubicin-induced oxidative stress, apoptosis, fibrosis, and cardiac dysfunction in mice by downregulating PTEN and activating the AKT pathway.
Does miR-495-3p protect against doxorubicin-induced cardiotoxicity in preclinical models?
miR-495-3p acts as an endogenous protectant against doxorubicin-induced cardiotoxicity by targeting PTEN and activating the AKT pathway in preclinical models.
Doxorubicin (Dox) is a broad-spectrum antitumour agent; however, its clinical application is impeded due to the cumulative cardiotoxicity. The present study aims to investigate the role and underlying mechanisms of microRNA-495-3p (miR-495-3p) in Dox-induced cardiotoxicity. Herein, we found that cardiac miR-495-3p expression was significantly decreased in Dox-treated hearts, and that the miR-495-3p agomir could prevent oxidative stress, cell apoptosis, cardiac mass loss, fibrosis and cardiac dysfunction upon Dox stimulation. In contrast, the miR-495-3p antagomir dramatically aggravated Dox-induced cardiotoxicity in mice. Besides, we found that the miR-495-3p agomir attenuated, while the miR-495-3p antagomir exacerbated Dox-induced oxidative stress and cellular injury in vitro. Mechanistically, we demonstrated that miR-495-3p directly bound to the 3'-untranslational region of phosphate and tension homology deleted on chromosome ten (PTEN), downregulated PTEN expression and subsequently activated protein kinase B (PKB/AKT) pathway, and that PTEN overexpression or AKT inhibition completely abolished the cardioprotective effects of the miR-495-3p agomir. Our study for the first time identify miR-495-3p as an endogenous protectant against Dox-induced cardiotoxicity through activating AKT pathway in vivo and in vitro.
Meng et al. (Sun,) conducted a other in Doxorubicin-induced cardiotoxicity. miR-495-3p agomir vs. Control / Doxorubicin alone was evaluated on Doxorubicin-induced cardiotoxicity (oxidative stress, cell apoptosis, cardiac mass loss, fibrosis, and cardiac dysfunction). The miR-495-3p agomir prevented doxorubicin-induced oxidative stress, apoptosis, fibrosis, and cardiac dysfunction in mice by downregulating PTEN and activating the AKT pathway.