MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations
Abstract Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FH...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-022-02714-6 |
| _version_ | 1811344912688349184 |
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| author | Li-rong Lin Xue-qun Hu Li-hong Lu Jia-zhen Dai Ning-ning Lin Re-hua Wang Zhang-xin Xie Xue-mei Chen |
| author_facet | Li-rong Lin Xue-qun Hu Li-hong Lu Jia-zhen Dai Ning-ning Lin Re-hua Wang Zhang-xin Xie Xue-mei Chen |
| author_sort | Li-rong Lin |
| collection | DOAJ |
| description | Abstract Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a “malignant” phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy. |
| first_indexed | 2024-04-13T19:55:13Z |
| format | Article |
| id | doaj.art-0c0b08401d1849309163f73c6d910584 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-04-13T19:55:13Z |
| publishDate | 2022-06-01 |
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| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-0c0b08401d1849309163f73c6d9105842022-12-22T02:32:21ZengBMCBMC Cardiovascular Disorders1471-22612022-06-012211910.1186/s12872-022-02714-6MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutationsLi-rong Lin0Xue-qun Hu1Li-hong Lu2Jia-zhen Dai3Ning-ning Lin4Re-hua Wang5Zhang-xin Xie6Xue-mei Chen7Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityAbstract Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a “malignant” phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy.https://doi.org/10.1186/s12872-022-02714-6Familial hypertrophic cardiomyopathyMYBPC3Gene mutationMicroRNA-sequencing |
| spellingShingle | Li-rong Lin Xue-qun Hu Li-hong Lu Jia-zhen Dai Ning-ning Lin Re-hua Wang Zhang-xin Xie Xue-mei Chen MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations BMC Cardiovascular Disorders Familial hypertrophic cardiomyopathy MYBPC3 Gene mutation MicroRNA-sequencing |
| title | MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations |
| title_full | MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations |
| title_fullStr | MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations |
| title_full_unstemmed | MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations |
| title_short | MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations |
| title_sort | microrna expression profiles in familial hypertrophic cardiomyopathy with myosin binding protein c3 mybpc3 gene mutations |
| topic | Familial hypertrophic cardiomyopathy MYBPC3 Gene mutation MicroRNA-sequencing |
| url | https://doi.org/10.1186/s12872-022-02714-6 |
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