Nucleolin protects against doxorubicin-induced cardiotoxicity via upregulating microRNA-21

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Nucleolin is a key protein involved in numerous cellular functions.
• Previous research indicated nucleolin's protective role in myocardial ischemia-reperfusion injury.
• Doxorubicin (DOX) is a widely used chemotherapy agent known to cause cardiotoxicity.

Purpose of the Study:

• To investigate the role of nucleolin in doxorubicin (DOX)-induced cardiotoxicity.
• To elucidate the molecular mechanisms underlying nucleolin's effect on DOX-induced cardiac injury.
• To explore nucleolin as a potential therapeutic target for mitigating DOX cardiotoxicity.

Main Methods:

• Assessed nucleolin expression in hearts subjected to DOX injury in vivo and in vitro.
• Utilized gene transfection and RNA interference in cardiomyocytes to study nucleolin function.
• Generated cardiac-myocyte-specific nucleolin transgenic mice.
• Investigated the effect of microRNA (miRNA)-21 inhibition on DOX-induced injury.

Main Results:

• Doxorubicin administration significantly increased nucleolin expression.
• Nucleolin overexpression protected cardiomyocytes from DOX-induced injury, while ablation sensitized them.
• Cardiac-specific nucleolin transgenic mice exhibited enhanced resistance to DOX injury.
• Nucleolin was found to upregulate miRNA-21 expression, and miRNA-21 inhibition abolished nucleolin's protective effects.

Conclusions:

• Nucleolin plays a protective role against DOX-induced cardiotoxicity.
• The protective mechanism involves the upregulation of miRNA-21.
• Nucleolin represents a promising therapeutic target for managing DOX-induced cardiac dysfunction.