X Guo1, Q Chang2, H Pei1, X Sun1, X Qian1, C Tian1, H Lin1. 1. Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100037, People's Republic of China. 2. Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100037, People's Republic of China. Electronic address: cqfuwai@126.com.
Abstract
OBJECTIVE/ BACKGROUND: Long non-coding RNA (lncRNA) play important roles in many diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA network and dissect lncRNAs that might contribute to the pathogenesis of STAA. METHODS: Differentially expressed lncRNAs and mRNAs between four ascending aortic specimens derived from STAA and four controls from patients who had undergone coronary artery bypass graft (CABG) were identified by microarray analysis. Gene Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented with differentially expressed genes. An lncRNA in the correlation network HOX transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR expression was examined by quantitative real time polymerase chain reaction in STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n = 2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role in apoptosis, cell proliferation, and expression of collagen types I and III. RESULTS: Five percent of lncRNAs were significantly differentially expressed in STAA patient samples compared with controls. GO enrichment analysis suggested differentially expressed genes were significantly enriched in the process of extracellular matrix organisation and leukocyte migration. lncRNA-mRNA interaction network revealed HOTAIR was associated with genes involved in extracellular matrix organisation. Moreover, HOTAIR expression was significantly decreased in STAA specimens and it negatively correlated with aortic diameter. HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation. Furthermore, both mRNA and protein levels of collagen types I and III expression were suppressed after HOTAIR knockdown. CONCLUSION: Transcriptomic and lncRNA-mRNA correlation analysis revealed HOTAIR was downregulated in STAA and associated with genes involved in extracellular matrix remodelling. In vitro experiments confirmed that knockdown of HOTAIR could induce apoptosis and suppress collagen types I and III expression in human aortic smooth muscle cells.
OBJECTIVE/ BACKGROUND: Long non-coding RNA (lncRNA) play important roles in many diseases. However, their roles in sporadic thoracic aortic aneurysm (STAA) are unclear. Therefore, the objective of this study was to construct an lncRNA-mRNA network and dissect lncRNAs that might contribute to the pathogenesis of STAA. METHODS: Differentially expressed lncRNAs and mRNAs between four ascending aortic specimens derived from STAA and four controls from patients who had undergone coronary artery bypass graft (CABG) were identified by microarray analysis. Gene Ontology (GO) enrichment and lncRNA-mRNA correlation analysis were implemented with differentially expressed genes. An lncRNA in the correlation network HOX transcript antisense intergenic RNA (HOTAIR) was selected as a candidate. HOTAIR expression was examined by quantitative real time polymerase chain reaction in STAA (n = 24) and controls (n = 24 [CABG, n = 22; heart transplant donors, n = 2]). HOTAIR expression was knocked down with siRNA in order to evaluate its role in apoptosis, cell proliferation, and expression of collagen types I and III. RESULTS: Five percent of lncRNAs were significantly differentially expressed in STAA patient samples compared with controls. GO enrichment analysis suggested differentially expressed genes were significantly enriched in the process of extracellular matrix organisation and leukocyte migration. lncRNA-mRNA interaction network revealed HOTAIR was associated with genes involved in extracellular matrix organisation. Moreover, HOTAIR expression was significantly decreased in STAA specimens and it negatively correlated with aortic diameter. HOTAIR knockdown induced early and late apoptosis and reduced cell proliferation. Furthermore, both mRNA and protein levels of collagen types I and III expression were suppressed after HOTAIR knockdown. CONCLUSION: Transcriptomic and lncRNA-mRNA correlation analysis revealed HOTAIR was downregulated in STAA and associated with genes involved in extracellular matrix remodelling. In vitro experiments confirmed that knockdown of HOTAIR could induce apoptosis and suppress collagen types I and III expression in human aortic smooth muscle cells.
Authors: Stefanie S Portelli; Elizabeth N Robertson; Cassandra Malecki; Kiersten A Liddy; Brett D Hambly; Richmond W Jeremy Journal: Biophys Rev Date: 2018-09-28