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Circular RNA expression profiles in the plasma of patients with infantile hemangioma determined using microarray analysis.

ABSTRACT: Circular RNAs (circRNAs) are noncoding RNAs that have important roles in tumor progression. Previous studies have examined the circRNAs involved in infantile hemangioma (IH) tumors. The present study compared the circRNA levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control subjects. Expression of the identified differentially expressed circRNAs was verified using reverse transcription-quantitative PCR (RT-qPCR) and a bioinformatics analysis was performed to predict the microRNAs targeted by the validated circRNAs. From the circRNA expression profiles in the plasma of patients with IHs, 128 differentially expressed circRNAs were identified, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs [Homo sapiens (hsa)_circRNA_101566, hsa_circRNA_103546 and hsa_circRNA_103573] was verified using RT-qPCR. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that all identified networks participated in angiogenesis and tumor formation and progression. It was determined that hsa_circRNA_101566, which is able to regulate the mTOR signaling pathway, may be an important regulatory molecule in IH development and that targeting of hsa_miR_520c is able to indirectly regulate the vascular endothelial growth factor signaling pathway. Further studies are required to clarify these effects and the underlying mechanisms.

SUBMITTER: Li Z

PROVIDER: S-EPMC8097215 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Circular RNAs (circRNAs) are noncoding RNAs that play important roles in tumor progression. Few studies have examined the circRNAs involved in infantile hemangioma (IH) progression. This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that all identified networks participated in angiogenesis and tumor formation and progression. We found that hsa_circRNA_101566, which can regulate the mammalian target of rapamycin signaling pathway, may be an important regulatory molecule in IH development and that targeting of hsa_miR_520c can indirectly regulate the vascular endothelial growth factor signaling pathway. Further studies are needed to clarify these effects and the underlying mechanisms.

Project description:Background Propranolol is a first-line clinical drug for infantile haemangiomas (IH) therapy. Nevertheless, resistance to propranolol is observed in some patients with IH. Circular RNAs (circRNAs) has been increasingly reported to act as a pivotal regulator in tumor progression. However, the underlying mechanism of circRNAs in IH remains unclear. Methods Quantitative real-time polymerase chain reaction was performed to detect Circ_0000915, miR-890 and RNF187 expression. Protein levels were determined using western blot. CCK-8 assay was used to measure cell proliferation. Caspase-3 activity assay and flow cytometry were conducted to determine cell apoptosis. Luciferase reporter assay was carried out to assess the interaction between miR-890 and Circ_0000915 or RNF187. Chromatin immunoprecipitation assay was performed to detect the interaction between STAT3 and Circ_0000915 promoter. Biotin pull-down assay was used to detect the direct interaction between miR-890 and Circ_0000915. In vivo experiments were performed to measure tumor formation. Results Here, we discovered depletion of Circ_0000915 increased propranolol sensitivity of haemangioma derived stem cells (HemSCs) both in vitro and in vivo, whereas forced expression of Circ_0000915 exhibited opposite effects. Mechanistically, Circ_0000915, transcriptionally induced by IL-6/STAT3 pathway, competed with RNF187 for the biding site in miR-890, led to upregulation of RNF187 by acting as a miR-890 “sponge”. Furthermore, silence of miR-890 reversed increased propranolol sensitivity of HemSCs due to Circ_0000915 ablation. Moreover, increased Circ_0000915 and RNF187 levels were observed in IH tissues and positively associated with propranolol resistance, miR-890 exhibited an inverse expression pattern. Conclusion We thereby uncover the activation of IL-6/STAT3/Circ_0000915/miR-890/RNF187 axis in propranolol resistance of IH, and provide therapeutic implications for patients of IH with propranolol resistance. Supplementary Information The online version contains supplementary material available at 10.1186/s40246-022-00416-w.

Project description:BackgroundCircular RNA (circRNA) is one type of noncoding RNA that forms a covalently closed continuous loop. Similar to long noncoding RNA (lncRNA), circRNA can act as microRNA (miRNA) 'sponges' to regulate gene expression, and its abnormal expression is related to diseases such as atherosclerosis, nervous system disorders and cancer. So far, there have been no systematic studies on circRNA abundance and expression profiles in human adult and fetal tissues.ResultsWe explored circRNA expression profiles using RNA-seq data for six adult and fetal normal tissues (colon, heart, kidney, liver, lung, and stomach) and four gland normal tissues (adrenal gland, mammary gland, pancreas, and thyroid gland). A total of 8120, 25,933 and 14,433 circRNAs were detected by at least two supporting junction reads in adult, fetal and gland tissues, respectively. Among them, 3092, 14,241 and 6879 circRNAs were novel when compared to the published results. In each adult tissue type, we found at least 1000 circRNAs, among which 36.97-50.04% were tissue-specific. We reported 33 circRNAs that were ubiquitously expressed in all the adult tissues we examined. To further explore the potential "housekeeping" function of these circRNAs, we constructed a circRNA-miRNA-mRNA regulatory network containing 17 circRNAs, 22 miRNAs and 90 mRNAs. Furthermore, we found that both the abundance and the relative expression level of circRNAs were higher in fetal tissue than adult tissue. The number of circRNAs in gland tissues, especially in mammary gland (9665 circRNA candidates), was higher than that of other adult tissues (1160-3777).ConclusionsWe systematically investigated circRNA expression in a variety of human adult and fetal tissues. Our observation of different expression level of circRNAs in adult and fetal tissues suggested that circRNAs might play their role in a tissue-specific and development-specific fashion. Analysis of circRNA-miRNA-mRNA network provided potential targets of circRNAs. High expression level of circRNAs in mammary gland might be attributed to the rich innervation.

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Circular RNA expression profiles in the plasma of patients with infantile hemangioma determined using microarray analysis.

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