CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

Abstract

Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.

Amplification of Long Noncoding RNA ZFAS1 Promotes Metastasis in Hepatocellular Carcinoma

“…The RNA pulldown was performed as previously described (18). Huh7 or HepG2 cells were transfected with biotinylated miRNA (40 nmol/L).…”

“…The interaction results in an increased level of Prkacb (cAMP-dependent protein kinase catalytic subunit beta), a target of miR-372. lncRNA-CARL suppresses anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation (18).…”

“Going Long”: Long Non-Coding RNAs as Biomarkers

“…5 lncRNAs display high organ and cell specificity and are involved in maintaining cell integrity. Previous analyses of cardiovascular lncRNAs were performed in cultured cells, [6][7][8] animal models, 9,10 and human heart biopsies. 10,11 Circulating lncRNAs have been suggested as potential biomarkers for cancer, but few studies have explored lncRNAs as biomarkers in the context of cardiovascular disease.…”

Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis

“…Given the observation that transgenic overexpression of miR-489 antagonized cardiac fibrosis after AngII treatment, it will be interesting to explore the role CHRF in cardiac fibrosis. 59 Besides the function of lncRNAs in cardiomyocyte hypertrophy, there is also evidence showing that lncRNAs regulate cardiomyocyte metabolism, 82 differentiation, and proliferation of cardiomyocytes. 83 In endothelial cells and smooth muscle cells, several lncRNAs (ie, MALAT1 and SENCR) have been shown to control migration and differentiation.…”