Dataset Information

LncRNA MIR503HG Targets miR-191-5p/PLCD1 Axis and Negatively Modulates Apoptosis, Extracellular Matrix Disruption, and Inflammation in Abdominal Aortic Aneurysm.

ABSTRACT: As the most prevalent subtype of aortic aneurysm, abdominal aortic aneurysm (AAA) features the apoptosis, extracellular matrix (ECM) disruption, and inflammation response of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) are crucial factors in AAA progression, while the investigations have not been fully explained. miR-191-5p upregulation is found in aortic aneurysm. However, its role in AAA has not been addressed. This research purposed to excavate the possible and associated molecular axis of miR-191-5p in AAA. In our study, miR-191-5p level was detected to be high in the tissues from AAA patients in comparison with the control group. After miR-191-5p expression was enhanced, cell viability was repressed, cell apoptosis was boosted, and ECM disruption and the inflammation response were fortified. Furthermore, the relationship among MIR503HG, miR-191-5p, and phospholipase C delta 1 (PLCD1) in VSMCs was disclosed via mechanism assays. Decreased MIR503HG lacked the inhibition on miR-191-5p targeting PLCD1, resulting in downregulation of PLCD1, which facilitated the progression of AAA. Thus, targeting MIR503HG/miR-191-5p/PLCD1 pathway will provide an additional method for the cure of AAA patients.

SUBMITTER: Tian Y

PROVIDER: S-EPMC10205412 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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lncRNA MIR503HG Targets miR-191-5p/PLCD1 Axis and Negatively Modulates Apoptosis, Extracellular Matrix Disruption, and Inflammation in Abdominal Aortic Aneurysm.

Tian Ye Y Li Xinxi X Bai Chao C Yang Zhenwei Z Zhang Lei L Luo Jun J Zhang Wenbin W

Mediators of inflammation 20230516

As the most prevalent subtype of aortic aneurysm, abdominal aortic aneurysm (AAA) features the apoptosis, extracellular matrix (ECM) disruption, and inflammation response of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) are crucial factors in AAA progression, while the investigations have not been fully explained. miR-191-5p upregulation is found in aortic aneurysm. However, its role in AAA has not been addressed. This research purposed to excavate the possible and associated mol ...[more]

PMID: 37228901

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Project description:The long noncoding RNA (lncRNA) CARMN (cardiac mesoderm enhancer associated noncoding RNA) is a highly conserved lncRNA that expresses primarily by smooth muscle cells (SMCs). Recent literature demonstrates that CARMN plays a critical role in the differentiation and maintaining of the contractile state of vascular SMCs. Because aortic SMCs show diminished contractile proteins in abdominal aortic aneurysms (AAAs), we hypothesize that the expression of CARMN is downregulated in the aortic wall affected by aneurysm. In this study, we analyzed publicly available single-cell or bulk RNA sequencing data comparing healthy and aneurysmal mouse aortic tissues. In both healthy and diseased aortas, Carmn expression was enriched in SMCs characterized by the high expression of SMC-specific contractile proteins including Myh11 and Acta2. Carmn expression levels varied among the sub-clusters of SMCs and consequently along the aortic tree. Comparing to the corresponding sham aorta, aortas from 3 distinct AAA models contained less Carmn. To validate the Carmn downregulation, we induced AAA using the Angiotensin II and CaCl2 models. In situ hybridization showed that Carmn mRNA located in the nuclei of SMCs and became downregulated within a few days following the aneurysm induction. Mechanistically, we tested whether Carmn expression is regulated by infiltrating macrophages --- the predominant inflammatory cells found in aneurysmal tissues --- by treating healthy mouse aortic SMCs with media conditioned by macrophages primed with pro-inflammatory or anti-inflammatory cytokines. PCR analysis showed that inflammatory macrophages reduced the expression of Carmn and contractile genes including Myh11 and Acta2. Taken together, our results from bioinformatic and experimental analyses demonstrate that Carmn is downregulated in different AAA models, likely by inflammatory macrophages. The negative regulation of Carmn in AAA tissues may explain at least in part the loss of SMC contractile state during the pathogenesis of this progressive degenerative disease.

Project description:ObjectiveThe aim of this study was to explore expression profiles of long noncoding RNA (lncRNA)-messenger RNA (mRNA) in abdominal aortic aneurysm (AAA) patients. Further, we explored the mechanisms by which lncRNA SNHG5 modulates the function of vascular smooth muscle cells (VSMC) in AAA.MethodsHuman gene expression profile GSE57691 dataset, was retrieved from Gene Expression Omnibus database. The dataset included gene expression array data of 49 AAA patients and 10 control aortic specimens from organ donors. To explore the main roles of the biological network, differentially expressed lncRNA and mRNAs in the aortic aneurysm (AAA) and normal aortic specimens were determined. Differentially expressed lncRNA and mRNAs were then used to construct a competing endogenous RNA (ceRNA) network using Cytoscape software, and the five key lncRNA were identified. SNHG5 which was significantly downregulated in the AAA was chosen and analysis showed that it regulates mir-205-5p and SMAD4 by binding to mir-205-5p. Double luciferase reporter gene assays, RNA immunoprecipitation, and RNA knockdown studies were used to establish the relationship between SNHG5 and mir-205-5p. Apoptosis rate was determined using flow cytometry, whereas cell proliferation was evaluated using Edu, and 24 well Transwell assay. Western blot analysis was used to determine protein expression levels.ResultsThe five differentially expressed lncRNAs were significantly correlated with 34 microRNAs and 112 mRNAs. mRNAs in the ceRNA network are implicated in protein binding, signal transduction, DNA and RNA transcription, development, and cell differentiation. SNHG5 was downregulated in the AAA and acts as a molecular sponge for mir-205. Downregulation of SNHG5 induces expression of mir-205-5p. Increased mir-205-5p expression level inhibits SMAD4 production, thus inhibiting proliferation and migration and promotes apoptosis of smooth muscle cells.ConclusionBioinformatics were used to explore molecular mechanism of AAA progression. The findings of this study show that lncRNA SNHG5 regulates proliferation and apoptosis of VSMC cells through modulation of the mir-205-5p/SMAD4 axis. Therefore, SNHG5 is a potential therapeutic target for AAA disease.

Dataset Information

LncRNA MIR503HG Targets miR-191-5p/PLCD1 Axis and Negatively Modulates Apoptosis, Extracellular Matrix Disruption, and Inflammation in Abdominal Aortic Aneurysm.

Publications

lncRNA MIR503HG Targets miR-191-5p/PLCD1 Axis and Negatively Modulates Apoptosis, Extracellular Matrix Disruption, and Inflammation in Abdominal Aortic Aneurysm.

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