CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis

Background. Circular RNA Transformation/Transcription Domain Associated Protein (circTRRAP, hsa_circ_0081241) was abnormally upregulated in acute myocardial infarction (AMI) patients. However, its biological role and functional mechanism in AMI remain to be researched. Methods. Human cardiomyocyte A...

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Main Authors: Yuan Zhang, Zhenggong Li, Jiao Wang, Hao Chen, Rui He, Hongkun Wu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Cardiovascular Therapeutics
Online Access:http://dx.doi.org/10.1155/2022/7125602
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author Yuan Zhang
Zhenggong Li
Jiao Wang
Hao Chen
Rui He
Hongkun Wu
author_facet Yuan Zhang
Zhenggong Li
Jiao Wang
Hao Chen
Rui He
Hongkun Wu
author_sort Yuan Zhang
collection DOAJ
description Background. Circular RNA Transformation/Transcription Domain Associated Protein (circTRRAP, hsa_circ_0081241) was abnormally upregulated in acute myocardial infarction (AMI) patients. However, its biological role and functional mechanism in AMI remain to be researched. Methods. Human cardiomyocyte AC16 was exposed to hypoxia to induce cell injury. Cell viability was detected through Cell Counting Kit-8. CircTRRAP, microRNA-370-3p (miR-370-3p), and Pro-Apoptotic WT1 Regulator (PAWR) levels were assayed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation analysis was performed via 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was assessed using flow cytometry and caspase-3 activity assay. The protein levels were measured through western blot. Enzyme-linked immunosorbent assay was used to examine the release of inflammatory cytokines. Oxidative stress was assessed by the commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assays were performed for the validation of target interaction. Results. CircTRRAP was highly expressed following hypoxia treatment in AC16 cells. Downregulation of circTRRAP promoted cell growth but inhibited apoptosis, inflammation, and oxidative stress in hypoxic cells. CircTRRAP could target miR-370-3p, and the regulatory effects of circTRRAP on the hypoxic cells were associated with the sponge function of miR-370-3p. PAWR served as the target for miR-370-3p, and it was regulated by circTRRAP/miR-370-3p axis. The protective role of miR-370-3p was achieved by downregulating the PAWR expression in hypoxia-treated AC16 cells. Conclusion. These findings demonstrated that silence of circTRRAP exerted the protection against the hypoxia-induced damages in cardiomyocytes through regulating the miR-370-3p and PAWR levels.
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spelling doaj-art-cd94a7e3fa7548c6922a4efa9ed48b2e2025-02-03T06:13:31ZengWileyCardiovascular Therapeutics1755-59222022-01-01202210.1155/2022/7125602CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR AxisYuan Zhang0Zhenggong Li1Jiao Wang2Hao Chen3Rui He4Hongkun Wu5Department of Cardiology CenterDepartment of Cardiology CenterDepartment of Cardiology CenterDepartment of Cardiology CenterDepartment of Cardiology CenterDepartment of Cardiology CenterBackground. Circular RNA Transformation/Transcription Domain Associated Protein (circTRRAP, hsa_circ_0081241) was abnormally upregulated in acute myocardial infarction (AMI) patients. However, its biological role and functional mechanism in AMI remain to be researched. Methods. Human cardiomyocyte AC16 was exposed to hypoxia to induce cell injury. Cell viability was detected through Cell Counting Kit-8. CircTRRAP, microRNA-370-3p (miR-370-3p), and Pro-Apoptotic WT1 Regulator (PAWR) levels were assayed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation analysis was performed via 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was assessed using flow cytometry and caspase-3 activity assay. The protein levels were measured through western blot. Enzyme-linked immunosorbent assay was used to examine the release of inflammatory cytokines. Oxidative stress was assessed by the commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assays were performed for the validation of target interaction. Results. CircTRRAP was highly expressed following hypoxia treatment in AC16 cells. Downregulation of circTRRAP promoted cell growth but inhibited apoptosis, inflammation, and oxidative stress in hypoxic cells. CircTRRAP could target miR-370-3p, and the regulatory effects of circTRRAP on the hypoxic cells were associated with the sponge function of miR-370-3p. PAWR served as the target for miR-370-3p, and it was regulated by circTRRAP/miR-370-3p axis. The protective role of miR-370-3p was achieved by downregulating the PAWR expression in hypoxia-treated AC16 cells. Conclusion. These findings demonstrated that silence of circTRRAP exerted the protection against the hypoxia-induced damages in cardiomyocytes through regulating the miR-370-3p and PAWR levels.http://dx.doi.org/10.1155/2022/7125602
spellingShingle Yuan Zhang
Zhenggong Li
Jiao Wang
Hao Chen
Rui He
Hongkun Wu
CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
Cardiovascular Therapeutics
title CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
title_full CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
title_fullStr CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
title_full_unstemmed CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
title_short CircTRRAP Knockdown Has Cardioprotective Function in Cardiomyocytes via the Signal Regulation of miR-370-3p/PAWR Axis
title_sort circtrrap knockdown has cardioprotective function in cardiomyocytes via the signal regulation of mir 370 3p pawr axis
url http://dx.doi.org/10.1155/2022/7125602
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