Project description:To determine the circRNA expression profile in IH and matched non-tumor tissues, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs in IH and matched non-tumor tissues.
Project description:Propranolol, a non-selective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at non-toxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab, to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 downregulation trigger the same pathway, suggesting that AQP1 is a major driver of betablockers antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TC). Functional in vitro studies showed that AQP1-positive telocytes play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely at least in part to a cross talk between lesional vascular cells and stromal telocytes.
Project description:Infantile hemangioma (IH) was one of the most common vascular tumors during childhood. Long non coding RNAs (lncRNAs) play great roles in angiogenesis; the involvement of lncRNAs in hemangioma remains unknown. We aim to investigate the differential expression of lncRNA between hemangioma and the adjacent normal tissues, with a view to studying the biological function of lncRNAs and their involvement in the pathogenesis of hemangioma. The differential lncRNAs expression profiles of hemangioma were established by lncRNA microarray. Bioinformatic analyses were applied for further study of these differentially expressed lncRNAs. A total of 2116 differentially expressed lncRNAs were identified, among these lncRNAs, 1259 were up-regulated and 857 were down-regulated more than two-fold.
Project description:As the most common vascular tumor during infancy, infantile hemangioma (IH) is clinically featured by a rapid proliferation phase of disorganized blood vessels and a subsequent spontaneous involution phase. Infantile hemangioma arises from a unique type of multipotent stem cells called hemangioma stem cells (HemSCs), which could differentiate into endothelial cells, pericytes and adipocytes in IH. However, the underlying mechanisms that regulate the cell fate determination of HemSCs are not well elucidated. Here, we identified KLF2 as a candidate transcription factor involved in the control of HemSCs differentiation. KLF2 was expressed in endothelial cells in proliferating IH and its expression diminished in adipocytes in involuting IH. KLF2 regualtes the proliferation, apopotosis and cell cycle progression in HemSCs. Moreover, KLF2 is a critical regulator in HemSCs that control their differentiation direction between endothelial cells and adipocytes. Knockdown of KLF2 inhibited the formation of blood vessels in vivo while accelerated the progress of adipogenesis. RNA-seq analysis suggested an induction of pro-adipogenic transcriptome in HemSCs upon KLF2 knockdown. Our data showed that KLF2 exhibited pleiotropic effects in regulating the biological behaviours of HemSCs, and was involved in the progression and involution of IH via determining the cell fate of HemSCs.
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: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: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:To determine the circRNA expression profile in gastrointestinal stromal tumor and matched non-tumor tissues, we used circRNA microArray analysis from Arraystar to examine the expression of circRNAs in gastrointestinal stromal tumor and matched non-tumor tissues.