Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Ethics
2.3. Myocardial Tissue Collection
2.4. RNA Extraction
2.5. RNA-Sequencing Analysis and Bioinformatics
2.6. Statistical Analysis
3. Results
3.1. ACM and Controls mRNA and miRNA Expression Profiles
3.2. Integrative Analysis Identified miRNA–mRNA Interaction for ACM
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALDH1 | Aldehyde dehydrogenase 1 family |
ACM | Arrhythmogenic cardiomyopathy |
BMPs | Bone morphogenetic proteins |
FN1 | Fibronectin |
ITGA5 | Integrin alpha 5 |
LP | Likely pathogenic |
miRNAs | MicroRNAs |
P | Pathogenic |
RV | Right ventricle |
SCD | Sudden cardiac death |
VUS | Variant of unknown significance |
References
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Sample | Phenotype | Gene | Protein | Nucleotide | dbSNP | gnomAD | ClinVar | ACMG |
---|---|---|---|---|---|---|---|---|
A1.R | ACM | FLNC | p.Arg1370Ter | c.4108C > T | rs1342121466 | 4/1450766 (0.0002%) | P | P |
A2.R | ACM | PKP2 DSG2 | p.Lys678ArgfsTer12 - | c.1881del c.523 + 2dup | rs764817683 rs2073126642 | NA 2/1451740 (0.0001%) | P VUS | P LP |
A4.R | ACM | PKP2 | p.Arg79Ter | c.235C > T | rs121434420 | 22/1577370 (0.001%) | LP | LP |
A6.R | ACM | TMEM43 | p.Ser358Leu | c.1073C > T | rs63750743 | 2/1461886 (0.0001%) | P | P |
B1.R | Control | - | - | - | - | - | - | - |
B2.R | Control | - | - | - | - | - | - | - |
B3.R | Control | - | - | - | - | - | - | - |
B5.R | Control | - | - | - | - | - | - | - |
Counts | |||||||
---|---|---|---|---|---|---|---|
Sample A1R | Sample A2R | Sample A4R | Sample A6R | Sample B1R | Sample B2R | Sample B5R | Gene Symbol |
268,147 | 333,296 | 319,027 | 39,769 | 149,975 | 223,451 | 826,406 | hsa-miR-1-3p |
110,587 | 91,623 | 77,600 | 49,265 | 38,476 | 47,353 | 180,699 | hsa-miR-143-3p |
26,647 | 70,761 | 71,180 | 51,234 | 63,687 | 81,431 | 160,503 | hsa-let-7a-5p |
27,074 | 45,652 | 39,339 | 18,103 | 25,298 | 41,027 | 111,000 | hsa-let-7f-5p |
25,882 | 52,083 | 43,790 | 25,771 | 21,360 | 25,545 | 85,002 | hsa-miR-26a-5p |
28,171 | 45,954 | 34,588 | 8582 | 17,237 | 12,243 | 56,518 | hsa-miR-30d-5p |
13,406 | 53,514 | 23,570 | 6424 | 8590 | 6284 | 34,382 | hsa-miR-133a-3p |
17,567 | 26,356 | 25,662 | 9669 | 11,579 | 12,041 | 39,905 | hsa-miR-24-3p |
17,871 | 16,799 | 14,542 | 4624 | 5552 | 4409 | 25,811 | hsa-miR-30a-5p |
10,120 | 14,886 | 12,774 | 4398 | 5066 | 5808 | 20,783 | hsa-miR-126-3p |
8811 | 13,206 | 12,865 | 4841 | 5804 | 6031 | 20,016 | hsa-miR-3074-5p |
4907 | 18,329 | 10,663 | 3449 | 6000 | 6092 | 18,876 | hsa-miR-30c-5p |
4371 | 12,644 | 10,991 | 5905 | 5633 | 5314 | 18,177 | hsa-miR-125b-5p |
4524 | 11,010 | 10,114 | 5501 | 6172 | 6933 | 18,603 | hsa-let-7g-5p |
6351 | 9710 | 7213 | 3066 | 3287 | 5284 | 15,622 | hsa-miR-27b-3p |
2106 | 7043 | 6079 | 2008 | 5542 | 7547 | 16,297 | hsa-miR-125a-5p |
3642 | 10,930 | 6973 | 2556 | 3627 | 4263 | 12,207 | hsa-miR-23b-3p |
4042 | 10,743 | 6644 | 1492 | 2689 | 2598 | 10,319 | hsa-miR-378a-3p |
2029 | 6048 | 4382 | 2687 | 4514 | 3126 | 9480 | hsa-miR-92a-3p |
2838 | 7362 | 5436 | 3769 | 2454 | 2178 | 6331 | hsa-miR-23a-3p |
3568 | 4394 | 3894 | 2565 | 3678 | 2126 | 9118 | hsa-miR-16-5p |
5040 | 4232 | 4240 | 1244 | 2229 | 2111 | 8984 | hsa-miR-22-3p |
2482 | 5222 | 4175 | 2261 | 1938 | 3021 | 8180 | hsa-miR-26b-5p |
2953 | 4191 | 2876 | 2977 | 4368 | 1119 | 7761 | hsa-miR-451a |
1496 | 3889 | 2983 | 1273 | 2556 | 2826 | 10,222 | hsa-miR-486-5p |
1496 | 3889 | 2983 | 1273 | 2556 | 2826 | 10,222 | hsa-miR-486-3p |
1872 | 3873 | 2903 | 2441 | 2029 | 2386 | 8070 | hsa-let-7i-5p |
1796 | 4135 | 3928 | 3380 | 1426 | 1829 | 7013 | hsa-miR-199a-3p |
817 | 2593 | 2470 | 3058 | 2414 | 3316 | 6456 | hsa-let-7c-5p |
3914 | 3111 | 3522 | 2173 | 1043 | 1457 | 5324 | hsa-miR-21-5p |
1840 | 3173 | 2807 | 1327 | 1658 | 1086 | 4991 | hsa-miR-103a-3p |
1840 | 3173 | 2807 | 1327 | 1658 | 1086 | 4991 | hsa-miR-103b |
2528 | 2397 | 2317 | 272 | 1096 | 1841 | 6253 | hsa-miR-499b-3p |
2528 | 2397 | 2317 | 272 | 1096 | 1840 | 6253 | hsa-miR-499a-5p |
1664 | 3486 | 2368 | 1272 | 1048 | 1185 | 5165 | hsa-miR-99b-5p |
1518 | 3079 | 2508 | 2021 | 848 | 946 | 4498 | hsa-miR-99a-5p |
2306 | 2956 | 2142 | 874 | 1256 | 1034 | 4838 | hsa-miR-181a-5p |
764 | 2217 | 1593 | 2737 | 1488 | 1875 | 4178 | hsa-let-7b-5p |
3068 | 2358 | 2571 | 523 | 976 | 664 | 4526 | hsa-miR-30e-5p |
1377 | 3945 | 2391 | 2752 | 671 | 508 | 2690 | hsa-miR-145-5p |
894 | 2055 | 1956 | 1684 | 712 | 909 | 3489 | hsa-miR-199b-3p |
1378 | 2869 | 1863 | 519 | 888 | 720 | 3044 | hsa-miR-30e-3p |
927 | 1861 | 1642 | 873 | 897 | 963 | 3769 | hsa-miR-423-3p |
927 | 1861 | 1642 | 873 | 897 | 963 | 3769 | hsa-miR-3184-5p |
912 | 1552 | 1243 | 2236 | 719 | 516 | 2638 | hsa-miR-100-5p |
951 | 2629 | 1462 | 1280 | 536 | 278 | 1718 | hsa-miR-140-3p |
1289 | 1841 | 1288 | 706 | 619 | 593 | 1990 | hsa-miR-27a-3p |
928 | 1654 | 1220 | 515 | 378 | 367 | 1917 | hsa-miR-151a-3p |
729 | 1841 | 1080 | 386 | 513 | 522 | 1785 | hsa-miR-30a-3p |
1095 | 1195 | 1101 | 748 | 560 | 487 | 1617 | hsa-miR-29a-3p |
913 | 1935 | 1215 | 466 | 387 | 249 | 1449 | hsa-miR-30b-5p |
603 | 1136 | 945 | 598 | 764 | 562 | 1959 | hsa-miR-191-5p |
267 | 588 | 593 | 469 | 840 | 1560 | 2217 | hsa-let-7e-5p |
543 | 1081 | 910 | 461 | 539 | 605 | 1712 | hsa-miR-151a-5p |
71 | 203 | 353 | 759 | 862 | 416 | 2886 | hsa-miR-10a-5p |
267 | 768 | 737 | 486 | 849 | 777 | 1490 | hsa-let-7d-5p |
431 | 821 | 735 | 377 | 481 | 704 | 1800 | hsa-miR-98-5p |
96 | 163 | 236 | 1239 | 872 | 287 | 1942 | hsa-miR-10b-5p |
495 | 983 | 831 | 383 | 366 | 320 | 1333 | hsa-miR-148a-3p |
Pathway | This Study | Reported Literature |
---|---|---|
Adipogenesis | ✓ | [27,28] |
Apoptosis | ✓ | [29] |
Cardiac Electrophysiology | ✓ | [30,31] |
Cardiac Muscle Contraction | ✓ | [10,12] |
Cardiovascular System Development | [20] | |
Cell–Cell Adhesion | ✓ | [19,20,22] |
Chromatin Organization | [22] | |
Circulatory System Development | [20] | |
EMT Process | ✓ | [32] |
ER Stress | ✓ | [25] |
Extracellular Matrix | ✓ | [19,20] |
Inflammation | ✓ | [19,20] |
Lipid and Atherosclerosis | ✓ | [19] |
Lipid Metabolism | ✓ | [33] |
Mitochondrial Respiration | ✓ | [22] |
Oxidative Stress | ✓ | [23] |
Oxidized LDL-Dependent Pathway | [23] | |
Platelet Degranulation | [19] | |
Regulation of Protein Secretion | [22] | |
Retinoic Acid Metabolic Process | ✓ | [34] |
TGF-ß Signalling | ✓ | [35] |
Tissue Development | [20] |
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Bonet, F.; Campuzano, O.; Córdoba-Caballero, J.; Alcalde, M.; Sarquella-Brugada, G.; Braza-Boïls, A.; Brugada, R.; Hernández-Torres, F.; Quezada-Feijoo, M.; Ramos, M.; et al. Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy. Biomedicines 2024, 12, 1807. https://doi.org/10.3390/biomedicines12081807
Bonet F, Campuzano O, Córdoba-Caballero J, Alcalde M, Sarquella-Brugada G, Braza-Boïls A, Brugada R, Hernández-Torres F, Quezada-Feijoo M, Ramos M, et al. Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy. Biomedicines. 2024; 12(8):1807. https://doi.org/10.3390/biomedicines12081807
Chicago/Turabian StyleBonet, Fernando, Oscar Campuzano, José Córdoba-Caballero, Mireia Alcalde, Georgia Sarquella-Brugada, Aitana Braza-Boïls, Ramon Brugada, Francisco Hernández-Torres, Maribel Quezada-Feijoo, Monica Ramos, and et al. 2024. "Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy" Biomedicines 12, no. 8: 1807. https://doi.org/10.3390/biomedicines12081807
APA StyleBonet, F., Campuzano, O., Córdoba-Caballero, J., Alcalde, M., Sarquella-Brugada, G., Braza-Boïls, A., Brugada, R., Hernández-Torres, F., Quezada-Feijoo, M., Ramos, M., Mangas, A., Ranea, J. A. G., & Toro, R. (2024). Role of miRNA–mRNA Interactome in Pathophysiology of Arrhythmogenic Cardiomyopathy. Biomedicines, 12(8), 1807. https://doi.org/10.3390/biomedicines12081807