Dataset Information

Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs.

ABSTRACT: Circular RNAs represent a new type of non-coding RNA molecules that influence the occurrence and development of various human diseases by sponging microRNAs, although their roles in heart failure have not been clarified. In this study, peripheral blood samples from 5 patients with heart failure and 4 healthy volunteers were analyzed by next-generation sequencing (NGS) to screen for differentially expressed Circular RNAs. Fifty-six differentially expressed Circular RNAs were identified, of which 29 were up-regulated and 27 were down-regulated. Dysregulated expression of 6 Circular RNAs was verified by quantitative polymerase chain reaction (PCR) analysis, and hsa_circ_0097435 expression was confirmed to be significantly up-regulated in 40 patients with heart failure. Further study with extracted exosomes showed that hsa_circ_0097435 expression was significantly higher in patients with heart failure. In cardiomyocytes, hsa_circ_0097435 was up-regulated after doxorubicin treatment, promoting cardiomyocyte apoptosis. Hsa_circ_0097435 overexpression promoted cardiomyocyte apoptosis, and silencing hsa_circ_0097435 inhibited apoptosis. Moreover, RNA-pulldown experiments and AGO2-immunoprecipitation experiments revealed that hsa_circ_0097435 potentially served a role in heart failure by sponging multiple microRNAs. Collectively, these results suggest that hsa_circ_0097435 can be used as a biological blood marker and revealed a new pathway involved in regulating myocardial cell injury. Our findings may provide a rational basis for developing new treatments for heart failure.

SUBMITTER: Han J

PROVIDER: S-EPMC7076158 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs.

Han Jiaqi J Zhang Liwei L Hu Longgang L Yu Hua H Xu Fengqiang F Yang Bin B Zhang Rui R Zhang Yongtao Y An Yi Y

Frontiers in genetics 20200310

Circular RNAs represent a new type of non-coding RNA molecules that influence the occurrence and development of various human diseases by sponging microRNAs, although their roles in heart failure have not been clarified. In this study, peripheral blood samples from 5 patients with heart failure and 4 healthy volunteers were analyzed by next-generation sequencing (NGS) to screen for differentially expressed Circular RNAs. Fifty-six differentially expressed Circular RNAs were identified, of which ...[more]

PMID: 32211036

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Project description:Circular RNAs (circRNAs) have been identified from various tissues and species, but their regulatory functions during developmental processes are not well understood. We examined circRNA expression profiles of two developmental stages of bovine skeletal muscle (embryonic and adult musculus longissimus) to provide first insights into their potential involvement in bovine myogenesis. We identified 12 981 circRNAs and annotated them to the Bos taurus reference genome, including 530 circular intronic RNAs (ciRNAs). One parental gene could generate multiple circRNA isoforms, with only one or two isoforms being expressed at higher expression levels. Also, several host genes produced different isoforms when comparing development stages. Most circRNA candidates contained two to seven exons, and genomic distances to back-splicing sites were usually less than 50 kb. The length of upstream or downstream flanking introns was usually less than 105 nt (mean≈11 000 nt). Several circRNAs differed in abundance between developmental stages, and real-time quantitative PCR (qPCR) analysis largely confirmed differential expression of the 17 circRNAs included in this analysis. The second part of our study characterized the role of circLMO7-one of the most down-regulated circRNAs when comparing adult to embryonic muscle tissue-in bovine muscle development. Overexpression of circLMO7 inhibited the differentiation of primary bovine myoblasts, and it appears to function as a competing endogenous RNA for miR-378a-3p, whose involvement in bovine muscle development has been characterized beforehand. Congruent with our interpretation, circLMO7 increased the number of myoblasts in the S-phase of the cell cycle and decreased the proportion of cells in the G0/G1 phase. Moreover, it promoted the proliferation of myoblasts and protected them from apoptosis. Our study provides novel insights into the regulatory mechanisms underlying skeletal muscle development and identifies a number of circRNAs whose regulatory potential will need to be explored in the future.

Project description:BACKGROUND: Heart failure (HF) is the most common cause of morbidity and mortality in developed countries. Here, we identify biologically relevant transcripts that are significantly altered in the early phase of myocardial infarction and are associated with the development of post-myocardial infarction HF. METHODS: We collected peripheral blood samples from patients with ST-segment elevation myocardial infarction (STEMI): n?=?111 and n?=?41 patients from the study and validation groups, respectively. Control groups comprised patients with a stable coronary artery disease and without a history of myocardial infarction. Based on plasma NT-proBNP level and left ventricular ejection fraction parameters the STEMI patients were divided into HF and non-HF groups. Microarrays were used to analyze mRNA levels in peripheral blood mononuclear cells (PBMCs) isolated from the study group at four time points and control group. Microarray results were validated by RT-qPCR using whole blood RNA from the validation group. RESULTS: Samples from the first three time points (admission, discharge, and 1 month after AMI) were compared with the samples from the same patients collected 6 months after AMI (stable phase) and with the control group. The greatest differences in transcriptional profiles were observed on admission and they gradually stabilized during the follow-up. We have also identified a set of genes the expression of which on the first day of STEMI differed significantly between patients who developed HF after 6 months of observation and those who did not. RNASE1, FMN1, and JDP2 were selected for further analysis and their early up-regulation was confirmed in HF patients from both the study and validation groups. Significant correlations were found between expression levels of these biomarkers and clinical parameters. The receiver operating characteristic (ROC) curves indicated a good prognostic value of the genes chosen. CONCLUSIONS: This study demonstrates an altered gene expression profile in PBMCs during acute myocardial infarction and through the follow-up. The identified gene expression changes at the early phase of STEMI that differentiated the patients who developed HF from those who did not could serve as a convenient tool contributing to the prognosis of heart failure.

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Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs.

Publications

Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs.

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