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...
Saved in:
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2022-01-01
|
Series: | Cardiovascular Therapeutics |
Online Access: | http://dx.doi.org/10.1155/2022/7125602 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832548637225254912 |
---|---|
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. |
format | Article |
id | doaj-art-cd94a7e3fa7548c6922a4efa9ed48b2e |
institution | Kabale University |
issn | 1755-5922 |
language | English |
publishDate | 2022-01-01 |
publisher | Wiley |
record_format | Article |
series | Cardiovascular Therapeutics |
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 |
work_keys_str_mv | AT yuanzhang circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis AT zhenggongli circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis AT jiaowang circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis AT haochen circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis AT ruihe circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis AT hongkunwu circtrrapknockdownhascardioprotectivefunctionincardiomyocytesviathesignalregulationofmir3703ppawraxis |