Project description:Infantile haemangiomas (IH) are the most common soft-tissue tumours in infants. Several studies have demonstrated the importance of circular RNA (circRNA) for the regulation of various cancer cells. The present study aims to evaluate the functions and molecular mechanisms of circATP5SL in IH progression. In this study, we found that circATP5SL is significantly dysregulated in IH. We conducted Transwell, MTT, and flow cytometry analysis to evaluate the role of circATP5SL in IH cell proliferation, invasion, migration, and apoptosis. Meanwhile, by using subcellular distribution detection, as well as dual-luciferase reporter test and RIP analysis, it has been confirmed that miR-873-5p directly binds to the 3'UTR of IGF1R mRNA, thereby inhibiting the expression of IGF1R. Besides, circATP5SL promoted IGF1R expression by directly adsorbing miR-873-5p, an IGF1R inhibitor, thereby promoting cellular invasion, proliferation, and migration as well as inhibition of apoptosis. In summary, our study suggests that circATP5SL promotes IH progression by regulating IGF1R expression through adsorption of miR-873-5p, elucidating circATP5SL as a promising therapeutic target for the prognostication and treatment of IH.
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:Surgical specimens from children with infantile hemangioma or lymphatic malformations, as well as healthy appearing adjacent skin, were analyzed by microarray analysis of microRNA expression. Unsupervised hierarchical clustering was performed to identify microRNAs that were differentially expressed in IH compared to lymphatic malformations and skin 19 patients who underwent surgical excision of either a lymphatic malformation or infantile hemangioma were used in the study. 5 patients have multiple samples on the array and these duplicates are from different regions of the excised tissue or separate lesions as indicated. Tissue was snap frozen in liquid nitrogen and used for RNA extraction
Project description:ObjectiveCongenital haemangiomas (CHs) are rare, benign vascular tumours that are fully developed at birth. Three subtypes of CHs have been described based on clinical behaviour: rapidly involuting CHs (RICHs), non-involuting CHs (NICHs) and partially involuting CHs (PICHs). We explore in our study clinical, evolutionary and paraclinical characteristics of the three CH subtypes.DesignChildren with CH attending our department of paediatric dermatology at Bordeaux University Hospital over a 13-year period were retrospectively included. Epidemiological, clinical and evolutionary data, photographs and imaging results were reviewed. All available tissue samples were histologically examined.ResultsWe included 57 patients: 22 with RICH, 22 with NICH and 13 with PICH. Males predominated (ratio 1.7); the most common CH location was on the limbs. RICH, NICH and PICH exhibited overlapping characteristics; all were single telangiectatic lesions with pale peripheral halos. At birth, NICHs were flat but RICHs and PICHs bulky. The median age at complete RICH involution was 12 months. One-third of CHs that appeared RICH-like at birth underwent incomplete involution to become PICHs. Heart failure and thrombocytopenia were rare complications. PICHs were frequently ulcerated. Pain was common for NICH and PICH. The imaging and histological data of the three CH subtypes were rather similar.ConclusionsWe describe the characteristics and evolution of the three CH subtypes using a case series. Certain overlapping features were apparent, reinforcing the hypothesis that RICH, NICH and PICH lie on the same pathological spectrum.
Project description:Intramuscular haemangiomas are benign soft tissue tumours that are more frequently seen in children and young adults. As they may be difficult to diagnose clinically, imaging has an important role in the detection, diagnosis and preoperative planning of these lesions. Haemangiomas of the extremities may be classified into capillary, cavernous, venous and mixed types, with or without an arteriovenous shunt, depending on the predominant vascular channels. Nonvascular components such as fat, smooth muscle, fibrous tissue and thrombus may also be present. This pictorial essay highlights the imaging features of intramuscular haemangiomas, with an emphasis on magnetic resonance imaging.
Project description:Surgical specimens from children with infantile hemangioma or lymphatic malformations, as well as healthy appearing adjacent skin, were analyzed by microarray analysis of microRNA expression. Unsupervised hierarchical clustering was performed to identify microRNAs that were differentially expressed in IH compared to lymphatic malformations and skin
Project description:To determine the microRNA expression profile in IH and non-tumor tissues, we uesed miRNA 4.0 microarray form Affymetrix to examine the expression of microRNA in IH and non-tumor tissues
Project description:To introduce a new skin dose mapping software system for interventional fluoroscopy dose assessment and to analyze the benefits and limitations of patient-phantom matching.In this study, a new software system was developed for visualizing patient skin dose during interventional fluoroscopy procedures. The system works by translating the reference point air kerma to the location of the patient's skin, which is represented by a computational model. In order to orient the model with the x-ray source, geometric parameters found within the radiation dose structured report (RDSR) are used along with a limited number of in-clinic measurements. The output of the system is a visual indication of skin dose mapped onto an anthropomorphic model at a resolution of 5 mm. In order to determine if patient-dependent and patient-sculpted models increase accuracy, peak skin dose was calculated for each of 26 patient-specific models and compared with doses calculated using an elliptical stylized model, a reference hybrid model, a matched patient-dependent model and one patient-sculpted model. Results were analyzed in terms of a percent difference using the doses calculated using the patient-specific model as the true standard.Anthropometric matching, including the use of both patient-dependent and patient-sculpted phantoms, was shown most beneficial for left lateral and anterior-posterior projections. In these cases, the percent difference using a reference model was between 8 and 20%, using a patient-dependent model between 7 and 15%, and using a patient-sculpted model between 3 and 7%. Under the table tube configurations produced errors less than 5% in most situations due to the flattening affects of the table and pad, and the fact that table height is the main determination of source-to-skin distance for these configurations. In addition to these results, several skin dose maps were produced and a prototype display system was placed on the in-clinic monitor of an interventional fluoroscopy system.The skin dose mapping program developed in this work represents a new tool that, as the RDSR becomes available through automated export or real-time streaming, can provide the interventional physician information needed to modify behavior when clinically appropriate. The program is nonproprietary and transferable, and also functions independent to the software systems already installed on the control room workstation. The next step will be clinical implementation where the workflow will be optimized along with further analysis of real-time capabilities.