Angiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway.
Ontology highlight
ABSTRACT:
SUBMITTER: Sotomayor-Flores C
PROVIDER: S-EPMC7429871 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Primary cilium serves as a cellular “antenna” to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the Kupffer’s vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p.
2012-06-01 | GSE34846 | GEO
Project description:Primary cilium serves as a cellular M-bM-^@M-^\antennaM-bM-^@M-^] to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the KupfferM-bM-^@M-^Ys vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p. RPE1 cells were transfected with control (Ctrl) or miR-129-3p (M129) oligo for 72h, and harvested for RNA extraction and hybridization on Affymetrix microarrays. Two samples: RPE1-Ctrl, RPE1-M129
2012-05-31 | E-GEOD-34846 | biostudies-arrayexpress
Project description:The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.
| S-EPMC5087095 | biostudies-literature
Project description:BackgroundThis study was designed to explore the therapeutic effect and mechanism of action of Qishen Yiqi dropping pills (QYDP) in chronic heart failure (CHF) via a long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) axis. Here, the mechanism of action of the lncRNA terminal differentiation-induced non-coding RNA (TINCR), miR-193b-3p, and RAR-related orphan receptor A (RORA) mRNA was analyzed in an angiotensin (Ang) II-induced H9C2 cardiomyocyte hypertrophy model treated with QYDP.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the gene expression changes of lncRNA, miRNA, and mRNA in H9C2 induced by QYDP on Ang II. The Gene Expression Omnibus (GEO) was used to analyze differentially expressed genes (DEGs) potentially affecting CHF progression. Cell Counting Kit-8 (CCK-8) was used to analyze the effect of QYDP on the proliferation of H9C2, RNA pull-down was used to analyze the binding of lncRNA and miRNA, and dual luciferase was used to analyze the targeting of miRNA and lncRNA or mRNA.ResultsAng II induced TINCR and RORA downregulation, miR-193b-3p upregulation, and hypertrophy in the H9C2 cardiomyocytes, which were alleviated by QYDP. In contrast, TINCR inhibition reversed the effects of QYDP by increasing miR-193b-3p expression and downregulating RORA expression. According to subsequent double luciferase and RNA pull-down experiments, TINCR adsorbed miR-193b-3p by acting as a competitive endogenous RNA sponge and miR-193b-3p directly targeted RORA. Lastly, we showed that the Ang-II-induced inhibition of TINCR and RORA expression and promotion of cardiac hypertrophy were both reversed by a TINCR overexpression plasmid (ov-TINCR), whereas the effects of ov-TINCR were suppressed by a miR-193b-3p mimic.ConclusionsAdministration of QYDP improves Ang II-induced H9C2 cardiomyocyte hypertrophy and increase cell proliferation rate through the TINCR/miR-193b-3p/RORA axis.
| S-EPMC9745534 | biostudies-literature
Project description:The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.
| S-EPMC4941343 | biostudies-other
Project description:The present study reveals a link between protein arginine methyltransferase 5 (PRMT5) and Homebox A9 (HoxA9) in the regulation of cardiomyocyte hypertrophy. In cardiomyocyte hypertrophy induced by β-adrenergic receptor agonist isoprenaline (ISO), PRMT5 expression was decreased while HoxA9 was upregulated. Silencing of PRMT5 or inhibition of PRMT5 by its pharmacological inhibitor EPZ augmented the expressions of cardiomyocyte hypertrophic genes brain natriuretic peptide (BNP) and β-Myosin Heavy Chain (β-MHC), whereas overexpression of PRMT5 inhibited ISO-induced cardiomyocyte hypertrophy, suggesting that PRMT5 ameliorates cardiomyocyte hypertrophy. On the contrary, HoxA9 promoted cardiomyocyte hypertrophy, as implied by the gain-of-function and loss-of-function experiments. HoxA9 was involved in the regulation of PRMT5 in cardiomyocyte hypertrophy, since HoxA9 knockdown prevented si-RPMT5-induced cardiomyocyte hypertrophy, and HoxA9 expression impaired the anti-hypertrophic effect of PRMT5. Co-immunoprecipitation experiments revealed that there were physical interactions between PRMT5 and HoxA9. The symmetric dimethylation level of HoxA9 was decreased by ISO or EPZ treatment, suggesting that HoxA9 is methylated by PRMT5. Additionally, PRMT5 repressed the expression of HoxA9. Chromatin immunoprecipitation (ChIP) assay demonstrated that HoxA9 could bind to the promoter of BNP, and that this binding affinity was further enhanced by ISO or EPZ. In conclusion, this study suggests that PRMT5 symmetric dimethylates HoxA9 and represses HoxA9 expression, thus impairing its binding to BNP promoter and ultimately protecting against cardiomyocyte hypertrophy. These findings provide a novel insight of the mechanism underlying the cardiac protective effect of PRMT5, and suggest potential therapeutic strategies of PRMT5 activation or HoxA9 inhibition in treatment of cardiac hypertrophy.
| S-EPMC7793800 | biostudies-literature
Project description:Cardiac hypertrophy mainly predicts heart failure and is highly linked with sudden loss of lives. MicroRNAs (miRNAs) play essential roles in the development of cardiac hypertrophy through binding to corresponding mRNA targets. In this study, in order to investigate the roles of two mature forms of miRNA-195, miR-195-3p, and miR-195-5p, in vitro and in vivo models of cardiac hypertrophy were established by applying angiotensin II (Ang II) to H9c2 cardiomyocytes and infusing chronic Ang II to mice, respectively. We found that miR-195-5p was evidently equally upregulated in the in vitro and in vivo studies of cardiac hypertrophy induced by Ang II. High expressed miR-195-5p could adequately promote hypertrophy, whereas the suppression of miR-195-5p prevented hypertrophy of H9c2 cardiomyocytes under Ang II treatment. Furthermore, the luciferase reporter system demonstrated that MFN2 and FBWX7 were target genes of miR-195-5p, which negatively regulated the expression of these two genes in H9c2 cells. By contrast, in both models, expression of miR-195-3p was only slightly changed without statistical significance. In addition, we observed a trend towards decreased expression of hypertrophic markers by overexpressing miR-195-3p in AngII-treated H9c2 cardiomyocytes in vitro. Taken together, our study indicates that miR-195-5p promotes cardiac hypertrophy via targeting MFN2 and FBXW7 and may provide promising therapeutic strategies for interfering cardiac hypertrophy.
| S-EPMC6614993 | biostudies-literature
Project description:MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO). In addition, we identified RE1-silencing transcription factor (REST) as a novel target of miR-218; it negatively regulated the expression of REST in hypertrophic cardiomyocytes and the TAC model. These results showed that miR-218 plays a crucial role in cardiomyocyte hypertrophy, likely via targeting REST, suggesting a potential candidate target for interfering hypertrophy.
| S-EPMC4926382 | biostudies-literature
Project description:Abnormal autophagy and oxidative stress contribute to angiotensin II- (Ang II-) induced cardiac hypertrophy and heart failure. We previously showed that Ang II increased Rap1GAP gene expression in cardiomyocytes associated with hypertrophy and autophagy disorders. Using real-time PCR and Western blot, we found that Rap1GAP expression was increased in the heart of Sprague Dawley (SD) rats infused by Ang II compared with saline infusion and in Ang II vs. vehicle-treated rat neonatal cardiomyocytes. Overexpression of Rap1GAP in cultured cardiomyocytes exacerbated Ang II-induced cardiomyocyte hypertrophy, reactive oxygen species (ROS) generation, and cell apoptosis and inhibited autophagy. The increased oxidative stress caused by Rap1GAP overexpression was inhibited by the treatment of autophagy agonists. Knockdown of Rap1GAP by siRNA markedly attenuated Ang II-induced cardiomyocyte hypertrophy and oxidative stress and enhanced autophagy. The AMPK/AKT/mTOR signaling pathway was inhibited by overexpression of Rap1GAP and activated by the knockdown of Rap1GAP. These results show that Rap1GAP-mediated pathway might be a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which could be a potential target for the future treatment of cardiac hypertrophy and heart failure.
| S-EPMC8062190 | biostudies-literature
Project description:Docetaxel is commonly used as an effective chemotherapeutic agent in breast cancer treatment, but the underlying mechanisms of drug resistance are not fully understood. The purpose of this study was to investigate the possible role of miR-129-3p in breast cancer cell resistance to docetaxel. MiR-129 and miR-129-3p inhibitor were transfected into breast cancer cells to investigate their effects on chemoresistance to docetaxel. The function of miR-129-3p was evaluated by apoptosis, cell proliferation, and cell cycle assays. We found that miR-129-3p was up-regulated in MDA-MB-231/Doc cells, concurrent with CP110 down-regulation, compared to the parental MDA-MB-231 cells. In vitro drug sensitivity assays demonstrated that miR-129-3p inhibition sensitized MDA-MB-231/Doc and MCF-7 cells to docetaxel, whereas miR-129 overexpression enhanced MDA-MB-231 and MCF-7 cell resistance to docetaxel. Ectopic miR-129 expression reduced CP110 expression and the luciferase activity of a CP110 3' untranslated region-based reporter construct in MDA-MB-231 cells, suggesting that CP110 is a direct miR-129-3p target. We demonstrated that restoration of CP110 expression in MDA-MB-231 and MCF-7 cells by miR-129 overexpression rendered the cells sensitive to docetaxel. In a nude xenograft model, miR-129 up-regulation significantly decreased MDA-MB-231 cells' response to docetaxel. Our findings suggest that miR-129-3p down-regulation potentially sensitizes breast cancer cells to docetaxel treatment.
| S-EPMC4614026 | biostudies-literature