Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease

In the present study, mitral valve tissues from three mitral stenosis patients with RHD by valve replacement and two healthy donors were harvested and conducted DNA methylation signature on PRKCA by MeDIP-qPCR. The presence of hypomethylated CpG islands at promoter and 5ʹ terminal of PRKCA was obser...

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Main Authors: Zan Xie, Qianli Wang, Shaojuan Hu
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Bioengineered
Subjects:
Online Access:http://dx.doi.org/10.1080/21655979.2021.1971482
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author Zan Xie
Qianli Wang
Shaojuan Hu
author_facet Zan Xie
Qianli Wang
Shaojuan Hu
author_sort Zan Xie
collection DOAJ
description In the present study, mitral valve tissues from three mitral stenosis patients with RHD by valve replacement and two healthy donors were harvested and conducted DNA methylation signature on PRKCA by MeDIP-qPCR. The presence of hypomethylated CpG islands at promoter and 5ʹ terminal of PRKCA was observed in RHD accompanied with highly expressed PRKCA and down-regulated antisense long non-coding RNA (lncRNA) PRKCA-AS1 compared to health control. Furthermore, the enrichments of DNMT1/3A/3B on PRKCA were detected by ChIP-qPCR assay in vivo and in human cardiomyocyte AC16 and RL-14 cells exposed to TNF-α in vitro, and both demonstrated that DNMT1 substantially contributed to DNA methylation. Additionally, PRKCA-AS1 was further determined to bind with promoter of PRKCA via 5ʹ terminal and interact with DNMT1 via 3ʹ terminal. Taken together, our results illuminated a novel regulatory mechanism of DNA methylation on regulating PRKCA transcription through lncRNA PRKCA-AS1, and shed light on the molecular pathogenesis of RHD occurrence.
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spelling doaj.art-40b3c6298c8d4f8cbfb05e36fa598ff42022-12-22T04:04:18ZengTaylor & Francis GroupBioengineered2165-59792165-59872021-01-011215904591510.1080/21655979.2021.19714821971482Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart diseaseZan Xie0Qianli Wang1Shaojuan Hu2The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityThe Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityThe Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityIn the present study, mitral valve tissues from three mitral stenosis patients with RHD by valve replacement and two healthy donors were harvested and conducted DNA methylation signature on PRKCA by MeDIP-qPCR. The presence of hypomethylated CpG islands at promoter and 5ʹ terminal of PRKCA was observed in RHD accompanied with highly expressed PRKCA and down-regulated antisense long non-coding RNA (lncRNA) PRKCA-AS1 compared to health control. Furthermore, the enrichments of DNMT1/3A/3B on PRKCA were detected by ChIP-qPCR assay in vivo and in human cardiomyocyte AC16 and RL-14 cells exposed to TNF-α in vitro, and both demonstrated that DNMT1 substantially contributed to DNA methylation. Additionally, PRKCA-AS1 was further determined to bind with promoter of PRKCA via 5ʹ terminal and interact with DNMT1 via 3ʹ terminal. Taken together, our results illuminated a novel regulatory mechanism of DNA methylation on regulating PRKCA transcription through lncRNA PRKCA-AS1, and shed light on the molecular pathogenesis of RHD occurrence.http://dx.doi.org/10.1080/21655979.2021.1971482rheumatic heart diseaseprotein kinase c alphadna methylationprkca-as1dnmt1
spellingShingle Zan Xie
Qianli Wang
Shaojuan Hu
Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
Bioengineered
rheumatic heart disease
protein kinase c alpha
dna methylation
prkca-as1
dnmt1
title Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
title_full Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
title_fullStr Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
title_full_unstemmed Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
title_short Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease
title_sort coordination of prkca prkca as1 interplay facilitates dna methyltransferase 1 recruitment on dna methylation to affect protein kinase c alpha transcription in mitral valve of rheumatic heart disease
topic rheumatic heart disease
protein kinase c alpha
dna methylation
prkca-as1
dnmt1
url http://dx.doi.org/10.1080/21655979.2021.1971482
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AT qianliwang coordinationofprkcaprkcaas1interplayfacilitatesdnamethyltransferase1recruitmentondnamethylationtoaffectproteinkinasecalphatranscriptioninmitralvalveofrheumaticheartdisease
AT shaojuanhu coordinationofprkcaprkcaas1interplayfacilitatesdnamethyltransferase1recruitmentondnamethylationtoaffectproteinkinasecalphatranscriptioninmitralvalveofrheumaticheartdisease