Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation
Abstract Background Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. Howev...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-024-01653-7 |
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| author | Ke-Xin Li Jia-Ru Li Sheng-Jia Zuo Xudong Li Xian-Tong Chen Pei-Yi Xiao Hui-Tao Li Ling Sun Tao Qian Hao-Min Zhang Dongxing Zhu Xi-Yong Yu Guojun Chen Xue-Yan Jiang |
| author_facet | Ke-Xin Li Jia-Ru Li Sheng-Jia Zuo Xudong Li Xian-Tong Chen Pei-Yi Xiao Hui-Tao Li Ling Sun Tao Qian Hao-Min Zhang Dongxing Zhu Xi-Yong Yu Guojun Chen Xue-Yan Jiang |
| author_sort | Ke-Xin Li |
| collection | DOAJ |
| description | Abstract Background Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. Methods and results miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. Conclusions Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD. |
| first_indexed | 2024-04-24T23:06:08Z |
| format | Article |
| id | doaj.art-9abde8e38db141908e0685e592b82b14 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-04-24T23:06:08Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-9abde8e38db141908e0685e592b82b142024-03-17T12:29:38ZengBMCClinical Epigenetics1868-70832024-03-0116112410.1186/s13148-024-01653-7Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylationKe-Xin Li0Jia-Ru Li1Sheng-Jia Zuo2Xudong Li3Xian-Tong Chen4Pei-Yi Xiao5Hui-Tao Li6Ling Sun7Tao Qian8Hao-Min Zhang9Dongxing Zhu10Xi-Yong Yu11Guojun Chen12Xue-Yan Jiang13Affiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityPeking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityShenzhen Maternity & Child Healthcare HospitalDepartment of Cardiac Pediatrics, Guangdong Provincial Cardiovascular Institute, Guangdong Provincial People’s Hospital, Southern Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Nanfang Hospital, Southern Medical UniversityAffiliated Qingyuan Hospital, Qingyuan People’s Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Science, Guangzhou Medical UniversityAbstract Background Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. Methods and results miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. Conclusions Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.https://doi.org/10.1186/s13148-024-01653-7MicroRNA-20b-5pCardiac differentiationTet methylcytosine dioxygenase 2 (TET2)DNA hydroxymethylation |
| spellingShingle | Ke-Xin Li Jia-Ru Li Sheng-Jia Zuo Xudong Li Xian-Tong Chen Pei-Yi Xiao Hui-Tao Li Ling Sun Tao Qian Hao-Min Zhang Dongxing Zhu Xi-Yong Yu Guojun Chen Xue-Yan Jiang Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation Clinical Epigenetics MicroRNA-20b-5p Cardiac differentiation Tet methylcytosine dioxygenase 2 (TET2) DNA hydroxymethylation |
| title | Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation |
| title_full | Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation |
| title_fullStr | Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation |
| title_full_unstemmed | Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation |
| title_short | Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation |
| title_sort | identification of mir 20b 5p as an inhibitory regulator in cardiac differentiation via tet2 and dna hydroxymethylation |
| topic | MicroRNA-20b-5p Cardiac differentiation Tet methylcytosine dioxygenase 2 (TET2) DNA hydroxymethylation |
| url | https://doi.org/10.1186/s13148-024-01653-7 |
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