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

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.08.090· OSTI ID:23103559

Li, Jing ^[1]; Li, Li ^[2]; Li, Xun ^[3]; Wu, Saizhu ^[1]

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1. Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515 (China)
2. State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 (China)
3. Guilin Detachment of Chinese People's Armed Police Force, Guilin, 541002 (China)

Highlights: • LncRNA LINC00339 was highly expressed in DOX stimulated primary rat cardiomyocytes and H9c2 cells. • Knockdown of LINC00339 significantly reduced primary rat cardiomyocytes and H9c2 cells proliferation and apoptosis. • LINC00339 acts as a critical pro-apoptosis lncRNA that aggravates DOX-induced cardiac remodeling by miR-484. Abnormally expressed long noncoding RNAs (lncRNAs) has been recognized as one of the key source in cardiac diseases. However, the role of lncRNA in doxorubicin (DOX)-induced cardiotoxicity remains largely unknown. In previous studies, we have screened some aberrantly expressed lncRNAs from an animal model for DOX-induced cardiotoxicity, and LINC00339 is one of the highly expressed lncRNA. In this study, we validated and further explored its regulatory mechanisms using in vitro model systems. Primary cultured myocardial cell (PC) and H9C2 cell line were treated with different concentrations of DOX and the expression of LINC00339 were markedly up-regulated. However, knockdown of endogenous LINC00339 by its siRNA improved cells proliferation activity and reduced cardiomyocyte apoptosis. Further experiments showed the opposite trend of expression between LINC00339 and miR-484. Bioinformatics analysis and luciferase reporter assay indicated that LINC00339 directly binds to miR-484. Moreover, miR-484 inhibitor abrogated the collagen synthesis inhibition induced by LINC00339. These findings reveal a novel function of the LINC00339/miR-484 axis in DOX-induced cardiotoxicity.

• OSTI ID: 23103559
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
DOXORUBICIN
LUCIFERASE
RATS
RNA