Similar Datasets
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
2023-01-25 | GSE215301 | GEO
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
2023-01-25 | GSE215302 | GEO
Project description:Suppression of RBFox2 by Multiple MiRNAs Contributed to Progressive Heart Failure
| PRJNA889732 | ENA
Project description:Heart failure is the final stage of various cardiovascular diseases and seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including the RNA binding protein RBFox2. It participates in multiple aspects of the regulation of cardiac function and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures, including mRNAs and miRNAs, in a mouse model of heart failure after TAC surgery. A global analysis showed that an asymmetric alternation in gene expression and a large-scale upregulation of miRNAs occurred in heart failure. An association analysis revealed that the latter not only contributed to the degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBFox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBFox2 was targeted by multiple miRNAs, including Let-7, miR-16, and miR-200b, which were significantly upregulated in heart failure. The overexpression of these miRNAs suppressed the RBFox2 protein and its downstream effects in cardiomyocytes, which was evidenced by the suppressed alternative splicing of the Enah gene and impaired E-C coupling via the repression of the Jph2 protein. The inhibition of Let-7, the most abundant miRNA family targeting RBFox2, could restore the RBFox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. In all, these findings revealed the molecular mechanism leading to RBFox2 depression in heart failure, and provided an approach to rescue RBFox2 through miRNA inhibition for the treatment of heart failure.
| S-EPMC9867119 | biostudies-literature
Project description:Suppression of RBFox2 by Multiple MiRNAs Contributed to Progressive Heart Failure (RNA-Seq)
| PRJNA889736 | ENA
Project description:Suppression of RBFox2 by Multiple MiRNAs Contributed to Progressive Heart Failure (small RNA-Seq)
| PRJNA889738 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-20 | GSE231587 | GEO
Project description:Heart performance relies on highly coordinated excitation-contraction (EC) coupling, and defects in this critical process may be exacerbated by additional genetic defects and/or environmental insults to cause eventual heart failure. Here we report a regulatory pathway consisting of the RNA binding protein RBFox2, a stress-induced microRNA miR-34a, and the essential EC coupler JPH2. In this pathway, initial cardiac defects diminish RBFox2 expression, which induces transcriptional repression of miR-34a, and elevated miR-34a targets Jph2 to impair EC coupling, which further manifests heart dysfunction, leading to progressive heart failure. The key contribution of miR-34a to this process is further established by administrating its mimic, which is sufficient to induce cardiac defects, and by using its antagomir to alleviate RBFox2 depletion-induced heart dysfunction. These findings elucidate a potential feed-forward mechanism to account for a critical transition to cardiac decompensation and suggest a potential therapeutic avenue against heart failure.
| S-EPMC6442575 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-04 | GSE240182 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-06 | E-GEOD-48112 | biostudies-arrayexpress