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| Status |
Public on Jul 31, 2022 |
| Title |
Circulating cardiac microRNA-FOXO3 axis safeguards against dilated cardiomyopathy |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Background - Cardiac microRNAs (miRNAs) could be released into circulation thus becoming circulating cardiac miRNAs, which are increasingly recognized as noninvasive and readily accessible biomarker for multiple heart diseases. A global loss of cardiac miRNAs due to dicer or dgcr8 depletion has been reported to lead to dilated cardiomyopathy (DCM). However, DCM-associated circulating miRNAs (DACMs) and their roles in regulating DCM progression remain largely unexplored.
Methods and Results - Through miRNA sequencing of human plasma procured from DCM patients and healthy control people, DCM was characterized with a unique expression pattern for circulating miRNAs. Among them, miR-26a-5p, miR-30c-5p, miR-126-5p, and miR-126-3p were all identified with dramatic reductions in DCM mouse myocardium as in the plasma of DCM patients. FOXO3, highlighted as a predicted common target gene, was experimentally demonstrated to be repressed within cardiomyocytes by these miRNAs except miR-26a-5p. Mechanistically, miRNA combination (miR-30c-5p, miR-126-5p, and miR-126-3p) significantly attenuated FOXO3-induced apoptosis and autophagy observed in cardiomyocytes as well as in DCM murine heart. Cardiac-specific knockout of FOXO3 conspicuously mitigated myocardial apoptosis and autophagy in DCM development. Moreover, stymieing the interaction between these miRNAs and FOXO3 mRNA extremely crippled the cardioprotection of these miRNAs against DCM progression.
Cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and autophagy, thereby maintaining cardiac homeostasis and potently preventing DCM development. These findings may provide serological clues for the noninvasive diagnosis of DCM in the future, and unambiguously shed new light on DCM pathogenesis and associated therapeutic targets
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| Overall design |
Ten Control human plasma RNA from N1~N10 and Ten DCM patient plasma RNA from T1,T3,T4,T5,T6,T7,T9,T10,T11,T13 respectively
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| Contributor(s) |
Cheng X, Jian D, Xing J |
| Citation missing |
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| Submission date |
Jul 28, 2022 |
| Last update date |
Jul 31, 2022 |
| Contact name |
xiaolei cheng |
| E-mail(s) |
chengduan1314@hotmail.com
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| Organization name |
Affiliated Drum Tower Hospital of Medical School of Nanjing University
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| Department |
Department of Anesthesiology
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| Street address |
321 Zhongshan Road
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| City |
Nanjing |
| State/province |
jiangsu |
| ZIP/Postal code |
210093 |
| Country |
China |
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| Platforms (1) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA863282 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE209991_rna_diff.txt.gz |
25.7 Kb |
(ftp)(http) |
TXT |
| GSE209991_rna_expression.txt.gz |
47.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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