Abstract
Long noncoding RNAs (lncRNAs) participate in various biological processes and cardiovascular diseases. Recently, a novel lncRNA XR_596701 was found to be differentially expressed in obstructive sleep apnea (OSA)-induced myocardial tissue compared to normal myocardial tissues. However, the pathological effect and regulatory mechanism of XR_596701 in intermittent hypoxia (IH)-mediated cardiomyocytes damage have not been studied. The subcellular localization of XR_596701 was determined by fluorescence in situ hybridization (FISH). Gene expressions of XR_596701 and miR-344b-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in IH-induced H9c2 cells. Cell proliferation was measured by 5-ethynyl-2′-deoxyuridine (EdU) staining assay. Cell apoptosis was detected by Hoechst 33342/PI staining and immunofluorescence (IF). Apoptotic protein of H9c2 cells was measured by western blot. The direct interaction between XR_596701 and miR-344b-5p as well as miR-344b-5p and Fas apoptotic inhibitory molecule 3 (FAIM3) were examined using dual-luciferase reporter assay. The significance of XR_596701 and miR-344b-5p on cell proliferation and apoptosis was evaluated by using gain-of-function and loss-of-function approaches. XR_596701 was upregulated, while miR-344b-5p downregulated in IH-induced H9c2 cells. Functionally, suppression of XR_596701 and overexpression of miR-344b-5p inhibited cell proliferation and promoted cell apoptosis in H9c2 cells. The roles of XR_596701 were achieved by sponging miR-344b-5p. And the function of miR-344b-5p was reversed by targeting FAIM3. Additionally, FAIM3 mediated IH-induced H9c2 cells damage by XR_596701. XR_596701 was serve as a novel lncRNA that indicated protective roles on proliferation and apoptosis of IH-induced H9c2 cells through the miR-344b-5p/FAIM3 axis.
Highlights
Obstructive sleep apnea (OSA), a common sleep disorder, is characterized by recurrent episodes of upper airway collapse during sleep, leading to recurrent events of nocturnal hypoxemia, hypercapnia and transient awakening [1]
Results demonstrated that Long noncoding RNAs (lncRNAs) XR_596701 was markedly elevated in the intermittent hypoxia (IH)-induced myocardial tissue [16]
Analysis based on high-scoring segment pair (HSP) distribution of genome (Fig. 1B) and HSP distribution of query sequence (Fig. 1C) demonstrated that XR_596701 is located on chromosome 17 in rat
Summary
Obstructive sleep apnea (OSA), a common sleep disorder, is characterized by recurrent episodes of upper airway collapse during sleep, leading to recurrent events of nocturnal hypoxemia, hypercapnia and transient awakening [1]. Several studies have focused on the relationship between OSA and cardiovascular (CV) diseases. Clinical studies have found that the prevalence of OSA in patients with coronary heart disease ranged from 30 to 58% and approximately 70% male hospitalized patients with myocardial infarction (MI) have OSA [2, 3]. OSA has been recognized a major risk factor for CV diseases [4]. It is likely that OSA negatively affects the pathological process of heart diseases through multiple complex mechanisms such as endothelial dysfunction and inflammation [5, 6], intermittent hypoxia (IH) in particular is the important player in OSA-associated CV diseases [7]. The potential mechanism between IH and CV disease is largely unknown
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