Long Noncoding RNA (lncRNA) n379519 Promotes Cardiac Fibrosis in Post-Infarct Myocardium by Targeting miR-30
Xiaxia Wang, Chunming Yong, Kai Yu, Renchao Yu, Rui Zhang, Lingfan Yu, Shan Li, Shanglang Cai
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
Med Sci Monit 2018; 24:3958-3965
Abnormally expressed long noncoding RNAs (lncRNAs) are recognized as one of the key causes of cardiac diseases. However, the role of lncRNA in cardiac fibrosis remains largely unknown.
MATERIAL AND METHODS: The experiment was divided into 4 groups: a sham operation group, a myocardial infarction (MI) group, a lentivirus group (LV-si-n379519), and a lentivirus control (LV-NC) group. The adenovirus expression vectors LV-si-n379519 and LV-NC were constructed and transfected into mice. Echocardiography, HE staining, and Masson staining were performed to detect the heart function and collagen volume fraction in each group. RT-PCR was used to detect the expression level of n379519, miR-30, collagen I, and collagen III. In vitro, cardiac fibroblasts (CFs) were cultured and the relationship between n379519 and miR-30 was verified using luciferase reporter vector, n379519 siRNA, and miR-30 inhibitor.
RESULTS: The expression of n379519 was markedly upregulated in the hearts of mice with MI and in the fibrotic CFs. Knockdown of endogenous n379519 by its siRNA improved the heart function and reduced collagen deposition and the process of cardiac fibrosis. Further experiments showed the opposite trend of expression between n379519 and miR-30. Bioinformatics analysis and luciferase reporter assay indicated that n379519 directly binds to miR-30. Moreover, miR-30 inhibitor abrogated the collagen synthesis inhibition induced by n379519.
CONCLUSIONS: These findings reveal a novel function of n379519-miR-30 axis as a negative regulator for the treatment of MI-induced cardiac fibrosis and the associated cardiac dysfunction.
Keywords: Endomyocardial Fibrosis, Myocardial Infarction, RNA, Long Noncoding