A long noncoding RNA NR_045363 controls cardiomyocyte proliferation and cardiac repair. (February 2019)

• Record Type: Journal Article
• Authors: Wang, Jue; Chen, Xianda; Shen, Danping; Ge, Donghui; Chen, Jiuling; Pei, Jianqiu; Li, Yandong; Yue, Zhang; Feng, Jie; Chu, Maoping; Nie, Yu
• Is Part Of: Journal of molecular and cellular cardiology. Volume 127(2019)
• Page Start: 105
• Page End: 114
• Publication Date: 2019-02
• Subjects: CM cardiomyocyte -- miRNA microRNA -- RNA ribonucleic acid -- lncRNA long non-coding RNA -- bp base pair -- cDNA complementary DNA -- RT reverse transcriptase -- PCR polymerase chain reaction -- RT-PCR real-time polymerase chain reaction -- MI myocardial infarction -- P postnatal day -- E embryonic day -- PBS Phosphate buffer solution -- DEPC Diethylpyrocarbonate -- AR apex resection -- AAV9 adeno-associated virus subtype 9 -- OE overexpression -- EdU 5-ethynyl-2′-deoxyuridine -- FBS Fetal bovine serum -- LAD left anterior descending coronary artery -- pH 3 phosphorylated histone H3; Long noncoding RNA -- Cardiomyocyte -- Proliferation -- Myocardial infarction -- Heart regeneration; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2018.12.005
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Long noncoding RNAs (lncRNAs) play important roles in the regulation of genes involved in cell proliferation. We have previously sought to more globally understand the differences of lncRNA expression between human fetal heart and adult heart to identify some functional lncRNAs which involve in the process of heart repair. We found that a highly conserved long noncoding RNA NR_045363 was mainly expressed in cardiomyocytes and rarely in non-cardiomyocytes. NR_045363 overexpression in 7-day-old mice heart could improve cardiac function and stimulate cardiomyocyte proliferation after myocardial infarction. Furthermore, NR_045363 knockdown inhibited proliferation of primary embryonic cardiomyocytes, while NR_045363 overexpression enhanced DNA synthesis and cytokinesis in neonatal cardiomyocytes in vitro. Mechanistic analysis revealed that NR_045363 promoted cardiomyocyte proliferation through interaction with miR-216a, which regulated the JAK2-STAT3 pathway. Our results showed that NR_045363 is a potent lncRNA modulator essential for cardiomyocyte proliferation. Graphical abstract: Unlabelled Image Highlights: NR_045363 plays a vital role in maintaining cardiomyocyte proliferative capacity shortly after birth. Applying recombinant AAV9:NR_045363 helps repairing injured mice hearts. NR_045363 exerts positive effects on cardiomyocyte proliferation by activating the miR-216a/JAK2-STAT3 pathway.