Long noncoding RNA LINC00339 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting MiR-484

Area of Science:

• Cardiovascular Biology
• Molecular Oncology
• RNA Biology

Background:

• Abnormal long noncoding RNA (lncRNA) expression is implicated in cardiac diseases.
• The specific role of lncRNAs in doxorubicin (DOX)-induced cardiotoxicity is not well understood.
• LINC00339 was identified as a highly expressed lncRNA in a DOX cardiotoxicity animal model.

Purpose of the Study:

• To investigate the regulatory mechanisms of LINC00339 in doxorubicin (DOX)-induced cardiotoxicity using in vitro models.
• To validate the role of LINC00339 in myocardial cell proliferation and apoptosis under DOX treatment.
• To elucidate the interaction between LINC00339 and microRNA-484 (miR-484) in the context of cardiotoxicity.

Main Methods:

• Primary cultured myocardial cells (PC) and H9C2 cell lines were treated with varying concentrations of DOX.
• LINC00339 expression levels were measured and modulated using small interfering RNA (siRNA).
• Cell proliferation, apoptosis, bioinformatics analysis, luciferase reporter assays, and miR-484 inhibitor experiments were performed.

Main Results:

• Doxorubicin treatment significantly upregulated LINC00339 expression in myocardial cells.
• Knockdown of LINC00339 using siRNA improved cell proliferation and reduced cardiomyocyte apoptosis.
• LINC00339 directly binds to miR-484, and miR-484 inhibition reversed the effects of LINC00339 on collagen synthesis.

Conclusions:

• LINC00339 plays a critical role in promoting doxorubicin-induced cardiotoxicity.
• The LINC00339/miR-484 axis is identified as a novel regulatory pathway in DOX-induced cardiotoxicity.
• This study reveals LINC00339 as a potential therapeutic target for mitigating chemotherapy-induced heart damage.