title: The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression.
abstract: OBJECTIVE
  Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis.
  
  
  METHODS
  Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets.
  
  
  RESULTS
  Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes.
  
  
  CONCLUSIONS
  Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, Shandong, China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Geng
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, Shandong, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Su
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Cai
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, Shandong, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000079962:RNA, Circular; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C549243:MIRN7 microRNA, mouse; D035683:MicroRNAs; D000079962:RNA, Circular; D016329:Sp1 Transcription Factor; D012313:RNA; D011065:Poly(ADP-ribose) Polymerases