MicroRNA-98 ameliorates doxorubicin-induced cardiotoxicity via regulating caspase-8 dependent Fas/RIP3 pathway

Area of Science:

• Molecular Biology
• Cardiology
• Pharmacology

Background:

• Cardiotoxicity is a major challenge limiting the use of doxorubicin (DOX) chemotherapy.
• The role of microRNAs (miRNAs) in DOX-induced cardiomyocyte death remains largely unexplored.

Purpose of the Study:

• To investigate the role of miR-98 in doxorubicin-induced cardiotoxicity.
• To elucidate the molecular mechanisms underlying miR-98's protective effects in cardiomyocytes.

Main Methods:

• Neonatal rat ventricular myocytes were treated with DOX.
• miR-98 expression levels were measured.
• Cell viability assays (MTT, LIVE/Dead, Viability/Cytotoxicity staining, Flow cytometry, Annexin V-FITC/PI staining) were performed.
• Protein expression of caspase-8, Fas, and RIP3 was analyzed.
• A specific caspase-8 inhibitor (Z-IETD-FMK) was used to validate the pathway.

Main Results:

• DOX treatment significantly increased miR-98 expression in cardiomyocytes.
• miR-98 mimic inhibited DOX-induced cardiomyocyte death.
• miR-98 mimic upregulated caspase-8 and downregulated Fas and RIP3 protein expression.
• The effects of miR-98 on Fas and RIP3 were dependent on caspase-8 activity.

Conclusions:

• miR-98 plays a protective role against DOX-induced cardiotoxicity.
• miR-98 exerts its protective effects by regulating the caspase-8-dependent Fas/RIP3 pathway.
• These findings highlight the therapeutic potential of miRNAs in managing DOX-induced cardiotoxicity.