THRIL mediates endothelial progenitor cells autophagy via AKT pathway and FUS
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RESEARCH ARTICLE
Molecular Medicine
Open Access
THRIL mediates endothelial progenitor cells autophagy via AKT pathway and FUS Jiandong Xiao1,2, Yuli Lu3 and Xinchun Yang1*
Abstract Background: This study focused on the roles of lncRNA THRIL in coronary atherosclerotic heart disease (CAD) through regulating AKT signaling pathway and directly interacting with FUS. Methods: QRT-PCR was conducted to detect the expression of THRIL in CAD blood samples and endothelial progenitor cells (EPCs). Cell autophagy of EPCs was examined through Cyto-ID Autophagy Detection Kit. CCK-8 assay and flow cytometry were carried out to assess cell viability and apoptosis under various interference conditions. Western blotting was conducted to detect the expression of interest proteins. The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by qRTPCR. The direct interactions between HCG18 and FUS was confirmed through RNA electrophoretic mobility shift assay (RNA EMSA) and RNA immunoprecipitation (RIP) assay. Results: THRIL was upregulated in CAD blood samples and EPCs. Knockdown of THRIL in EPCs promoted cell viability, inhibited cell autophagy and further suppressed the development of CAD. Over-expression of THRIL induced inactivation of AKT pathway, while knockdown of THRIL played reversed effects. THRIL directly interacted with FUS protein and knockdown of FUS reversed the over-expressing effect of THRIL on cell proliferation, autophagy and the status of AKT pathway. Conclusion: THRIL inhibits the proliferation and mediates autophagy of endothelial progenitor cells via AKT pathway and FUS. Keywords: THRIL, Coronary heart disease, AKT, FUS
Introduction Coronary atherosclerotic heart disease (CAD) is one of the chronic diseases with very high mortality rate due to the acceleration of population aging process (CorralDebrinski et al., 1992). The level of risk factors for cardiovascular disease (CVD) continues to increase all over the world (Becker, 1985). Moreover, the incidence of CAD and the resulting social and economic burden are increasing (Ornish et al., 1990). Although cruuent treatments such as medical treatment, percutaneous coronary intervention (PCI), and coronary artery bypass surgery * Correspondence: [email protected] 1 Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China Full list of author information is available at the end of the article
have improved the prognosis of CAD, the mortality rate remains high (Keys, 1975). It is urgent to explore the pathological mechanism of CAD, optimize the treatment strategy, and enable early diagnosis of CAD. Recently, autophagy has become a new research interest with the increased understanding of the pathogenesis of atherosclerosis. It has been reported that autophagy is closely related to cancer, neurodegenerative diseases, and CVD (Rebecca & Amaravadi, 2016; Deng et al., 2017). Autophagy is a process
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