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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Construction of a novel circRNA-miRNA-ferroptosis related mRNA network in ischemic stroke
Huirong Xie1, Yijie Huang2, Yanli Zhan3
1Department of Neurology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Clinical Research Center for Neurological Diseases, 289 Kuocang Road, Lishui, 323000, Zhejiang, China. xiehuirong_doctor@163.com.
Abstract:
Molecule alterations are important to explore the pathological mechanism of ischemic stroke (IS). Ferroptosis, a newly recognized type of regulated cell death, is related to IS. Identification of the interactions between circular RNA (circRNA), microRNA (miRNA) and ferroptosis related mRNA may be useful to understand the molecular mechanism of IS. The circRNA, miRNA and mRNA transcriptome data in IS, downloaded from the Gene Expression Omnibus (GEO) database, was used for differential expression analysis. Ferroptosis related mRNAs were identified from the FerrDb database, followed by construction of circRNA-miRNA-ferroptosis related mRNA network. Enrichment and protein-protein interaction analysis of mRNAs in circRNA-miRNA-mRNA network was performed, followed by expression validation by reverse transcriptase polymerase chain reaction and online dataset. A total of 694, 41 and 104 differentially expressed circRNAs, miRNAs and mRNAs were respectively identified in IS. Among which, dual specificity phosphatase 1 (DUSP1), nuclear receptor coactivator 4 (NCOA4) and solute carrier family 2 member 3 (SLC2A3) were the only three up-regulated ferroptosis related mRNAs. Moreover, DUSP1, NCOA4 and SLC2A3 were significantly up-regulated in IS after 3, 5 and 24 h of the attack. Based on these three ferroptosis related mRNAs, 4 circRNA-miRNA-ferroptosis related mRNA regulatory relationship pairs were identified in IS, including hsa_circ_0071036/hsa_circ_0039365/hsa_circ_0079347/hsa_circ_0008857-hsa-miR-122-5p-DUSP1, hsa_circ_0067717/hsa_circ_0003956/hsa_circ_0013729-hsa-miR-4446-3p-SLC2A3, hsa_circ_0059347/hsa_circ_0001414/hsa_circ_0049637-hsa-miR-885-3p-SLC2A3, and hsa_circ_0005633/hsa_circ_0004479-hsa-miR-4435-NCOA4. In addition, DUSP1 is involved in the signaling pathway of fluid shear stress and atherosclerosis. Relationship of regulatory action between circRNAs, miRNAs and ferroptosis related mRNAs may be associated with the development of IS.
Insights
Investigating molecular interactions in ischemic stroke (IS) reveals key regulatory networks involving circular RNA, microRNA, and ferroptosis-related mRNA. These findings enhance understanding of IS pathology and potential therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Ischemic stroke (IS) involves complex molecular alterations.
- Ferroptosis, a regulated cell death form, is implicated in IS pathogenesis.
- Understanding interactions between circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) is crucial for elucidating IS mechanisms.
Purpose of the Study:
- To identify and analyze the regulatory network of circRNA, miRNA, and ferroptosis-related mRNA in ischemic stroke.
- To explore the potential role of these interactions in the molecular mechanisms underlying IS.
Main Methods:
- Differential expression analysis of circRNA, miRNA, and mRNA transcriptome data from the Gene Expression Omnibus (GEO) database for IS.
- Identification of ferroptosis-related mRNAs using the FerrDb database.
- Construction and analysis of a circRNA-miRNA-ferroptosis related mRNA regulatory network.
Main Results:
- 694 differentially expressed circRNAs, 41 miRNAs, and 104 mRNAs were identified in IS.
- Dual specificity phosphatase 1 (DUSP1), nuclear receptor coactivator 4 (NCOA4), and solute carrier family 2 member 3 (SLC2A3) were the only upregulated ferroptosis-related mRNAs.
- Four circRNA-miRNA-ferroptosis related mRNA regulatory pairs were identified, suggesting their association with IS development.
Conclusions:
- The identified circRNA-miRNA-mRNA regulatory network provides insights into the molecular mechanisms of ischemic stroke.
- Specific regulatory relationships involving DUSP1, NCOA4, and SLC2A3 may play a significant role in IS progression.
- Further investigation into these interactions could reveal novel therapeutic strategies for ischemic stroke.

