Project description:We identified adipocyte enhancer binding protein 1 (AEBP1) as a novel tumor endothelial marker in colorectal cancer (CRC). To identify target genes of AEBP1 in endothelial cells, we knocked down AEBP1 in human umbilical vein endothelial cells (HUVECs). We found that genes associated with angiogenesis including aquaporin 1 (AQP1) and periostin (POSTN) are downregulated by AEBP1 knockdown in HUVECs, suggesting that AEBP1 may promote tumor angiogenesis through regulating these genes.
Project description:We identified adipocyte enhancer binding protein 1 (AEBP1) as a novel cancer-associated fibroblast (CAF) marker in oral squamous cell carcinoma (OSCC). To study the function of AEBP1 in CAFs, we knocked down AEBP1 in CAFs isolated from surgically resected primary OSCCs. We found that genes associated with cell cycle were significantly affected by AEBP1 knockdown in CAFs.
Project description:AEBP1 has been identified as a transcriptional repressor playing a significant role in adipogenesis. Recently, we have found that AEBP1 is specifically upregulated in primary glioblastoma. We have used gene silencing to identify genes perturbed upon AEBP1 downregulation and ChIP-chip technique to identify its genomic targets of binding and regulation to understand the un-annotated/undescribed role of this transcription factor in gliomagenesis. Cells either mock silenced or silenced using siRNA against AEBP1 were harvested at 46hrs post transfection. Gene expression was profiled for control and AEBP1 silenced cells. comparison of AEBP1/Rabbit IgG/ Glial cells
Project description:To study the potential target genes regulated by PML in endothelial cells, we carried out siRNA-mediated knockdown of PML in HUVEC cells. To eliminate the off-target effects of siRNAs, we utilized two different siRNAs. Only the genes changed in the same pattern following both siRNAs transfection are considered as potential PML-knockdown responsive genes.
Project description:To study the interaction effects between promyelocytic leukemia (PML) gene knockdown and tumor necrosis factor-alpha (TNFalpha) signaling in human umbilical vein endothelial cells (HUVECs), we transfected control or two independent PML siRNAs into HUVEC cells without or with 20 ng/mL TNFalpha treatment for 20 h. The total RNA was extracted for gene expression microarray analyses.
Project description:AEBP1 has been identified as a transcriptional repressor playing a significant role in adipogenesis. Recently, we have found that AEBP1 is specifically upregulated in primary glioblastoma. We have used gene silencing to identify genes perturbed upon AEBP1 downregulation and ChIP-chip technique to identify its genomic targets of binding and regulation to understand the un-annotated/undescribed role of this transcription factor in gliomagenesis.
Project description:Glioblastoma (GBM) is the most lethal primary brain tumor in adults with a median survival of around 15 months. A potential treatment strategy involves targeting glioma stem-like cells (GSCs) that are able to initiate, maintain, and repopulate the tumor mass. Here, we identify ACT001, a parthenolide derivative, targeting GSCs through regulation of adipocyte enhancer binding protein 1 (AEBP1) signaling.GSCs exhibit high response to ACT001 in compared with normal human astrocytes. AEBP1 is a putative target of ACT001 by RNA-Seq analysis, which expression associates with prognosis of GBM patients. Knockdown of AEBP1 inhibits GSC proliferation whereas ectopic expression of AEBP1 increases GSC proliferation and xenograft tumor growth. AEBP1 overexpression also attenuates ATC001-inhibited GSC orthotopic xenograft tumor growth. Treatment with ACT001 or PI3K inhibitor or AEBP1 depletion decreases AKT phosphorylation and GSC proliferation. However, constitutive AKT activation rescues ACT001 treatment or AEBP1 knockdown-inhibited cell proliferation. Additionally, ACT001 blocks TGF-β-activated AEBP1/AKT signaling in GSCs. ACT001 exhibits antitumor activity either as a single agent or in combination with SHP099, which provides significant survival benefits for GSC xenograft tumor -bearing animals.