Project description:Tmub1 is involved in liver regeneration and functions as a bridging protein in tumor cell proliferation. To investigate the transcriptional profile and potential biological processes affected by Tmub1 expression in normal rat hepatocytes, microarray and bioinformatics experiments were used to identify 127 mRNAs differentially expressed between Tmub1-overexpression, Tmub1-knockdown and normal BRL-3A cells (fold change ≥ 2.5, P < 0.05).
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:Time-course gene expression profiles were obtained from lung tissues of the rats treated with room air, intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days using CodeLink microarrays. Using a systems biology approach, we observed that two different mechanisms are involved in the lung responses to IH and SH: IH leads to increased G-protein coupled signaling-, ion transport-, neuronal- and steroid hormone receptor activities; whereas SH causes increased blood vessel morphogenesis and immune responses. Our results provide insight into molecular mechanisms underlying IH and SH. Keywords: gene expression array-based, count rats were treated with intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days; rats treated with room air were used as controls; gene expression profiles were obtained from these rats
Project description:Time-course gene expression profiles were obtained from lung tissues of the rats treated with room air, intermittent- (IH) or sustained hypoxia (SH) for 1, 3, 7, 14 and 30 days using CodeLink microarrays. Using a systems biology approach, we observed that two different mechanisms are involved in the lung responses to IH and SH: IH leads to increased G-protein coupled signaling-, ion transport-, neuronal- and steroid hormone receptor activities; whereas SH causes increased blood vessel morphogenesis and immune responses. Our results provide insight into molecular mechanisms underlying IH and SH. Keywords: gene expression array-based, count
Project description:Intermittent hypoxia (IH) in HeLa cell culture activates proinflammatory transcription factor NFκB, whereas chronic hypoxia (CH) does not. In order to determine whether IH may be linked to vascular inflammation, we developed a novel IH cell culture system and exposed HAEC (human aortic endothelial cells) to IH or CH. Keywords: Human Artery Endothelial Cells (HAEC)
Project description:Identification of the DNA binding landscape of the transcription factor regulatory factor X 7 (RFX7) in Nutlin-3a and DMSO control treated U2OS cells.
Project description:Identification of the DNA binding landscape of the transcription factor regulatory factor X 7 (RFX7) in Nutlin-3a and DMSO control treated HCT116 cells.
Project description:3T3L1 preadipocytes were treated with DMSO control and Nutlin-3a (prepared in DMSO) and total RNA extracted from the treated cells were subjected to illumina based RNA-seq to analyze and compare transcriptome to understand gene expression regulation influenced by p53 activation via Nutlin-3a treatment.
Project description:Identification of the DNA binding landscape of the transcription factor regulatory factor X 7 (RFX7) in Nutlin-3a and DMSO control treated RPE-1 cells.