Project description:Our previous study reported that IGFBP7 plays a role in maintaining mRNA stability of oncogenic lncRNA UBE2CP3 by RNA-RNA interaction. Clinical cohort studies had implied an oncogenic role of IGFBP7 in GC. However, the molecular mechanism of IGFBP7 in driving gastric cancer (GC) progression remains unknown. In this study, clinical analysis based on two independent cohort showed that IGFBP7 was positively associated with poor prognosis and macrophage infiltration in GC. Loss-of-function studies confirmed the oncogenic properties of IGFBP7 in regulating GC cell proliferation and invasion. Mechanismly, IGFBP7 was induced by epithelial-to-mesenchymal transition (EMT) signaling, since its expression was increased by TGF-beta treatment and reduced by overexpression of OVOL2 in GC. RNA sequencing, qRT-PCR, ELISA assay showed that IGFBP7 positively regulating FGF2 expression and secretion. Transcriptome analysis revealed that FGFR1 was downregulated in M1 macrophages but upregulated in M2 macrophages. Exogenous recombinant IGFBP7 protein in macrophages and GC cells further identified that IGFBP7 promotes macrophage polarization towards to a M2/TAM phenotype via FGF2/FGFR1/PI3K/AKT axis. Our finding highlights that IGFBP7 promotes GC by enhancing TAM infiltration through FGF2/FGFR1/PI3K/AKT axis.
Project description:Serine proteases dysregulation has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, we explored the biological function of PRSS23 in GC by RNA sequencing. Our data highlights that PRSS23 promotes GC progression by promoting macrophage infiltration via regulating FGF2 expression.
Project description:Cell co-culture experiments and bioinformatics analysis show that soluble FGF2 plays an important role in the cross-talking between CAF and tumor cells. This study aimed to explore the efffects of human recombinant FGF2 protein (20 ng/mL) on the transcriptome of GC cells.
Project description:Our data showed that UBE2CP3 was aberrantly upregulated in gastric cancer (GC), but its biofunction in GC is largely unknown to date. To explore the function of lncRNA UBE2CP3 in gastric cancer, loss-of-function and RNA sequencing studies were performed in SGC7901 cell line. The results showed that depletion of UBE2CP3 significantly decreased the expression of ITGA2. Interestingly, ITGA2 was also a target gene of miR-138. Our data showed that UBE2CP3 promotes GC progression through regulating miR-138/ITGA2 axis. Additionally, lncRNA UBE2CP3 could be stabilized by IGFBP7 mRNA. IGFBP7 depletion also significantly decreased ITGA2 expression.
Project description:We compared proteomic analysis of extracellular vesicles (EVs) secreted from human dermal fibroblasts, either control or stimulated by FGF2 and after immunoprecipitation with FGF2-coated beads to isolated FGF2-positive EVs.
Project description:Transcriptional profiling of mouse spermatogonial stem cells (SSCs) comparing control untreated SSCs with SSCs with exogenous FGF2 withdrawn and FGFR inhibitor SU5402 supplemented (-F+S). Results provide insight into the mechanisms of FGF2-supported in vitro self-renewal of SSCs.
Project description:NANOG has emerged as a central gatekeeper of pluripotency. Here we show that as human embryonic stem (ES) cells exit the pluripotent state, NANOG can play a key role in determining lineage outcome. It has previously been reported that BMPs can induce differentiation of human ES cells into extraembryonic lineages. Here we report that FGF2 switches BMP4 induced differentiation outcome to mesendoderm, characterized by the uniform expression of T (brachyury) and other primitive streak markers. Blocking the MEK-ERK pathway either by chemical inhibitors or by an ERK-specific phosphatase (DUSP6) blocks the FGF2-mediated lineage switch. Active MEK-ERK signaling prolongs NANOG expression during BMP-induced differentiation. Forced NANOG expression results in FGF independent BMP4 induction of mesendoderm, and knockdown of NANOG greatly reduces T induction. Together, our results demonstrate that FGF2 signaling switches the outcome of BMP4 induced differentiation of human ES cells by maintaining NANOG levels through the MEK-ERK pathway. There are three sets of expression data. Set 1 (14 samples) is 5day human ES cells (H1) differentiated with different concentrations of BMP4, in the presence or absence of FGF2. Set 2 (14 samples) is 50ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2. Set 3 (22 samples) is 5ng/mL of BMP4 induced H1 cells differentiation time course, with or without FGF2.
Project description:This series includes hES cell samples starved and re-stimulated with FGF2. Controls were FGF2-starved but not re-stimulated. Two independent experiments were carried out (one sample plus control each). Keywords: Growth factor stimulation experiment
Project description:We analyze the cortical transcriptome under physiological or FGF2-perturbed conditions. Using system biology approaches (DGE, WGCNA and kinase enrichment analysis) we identify networks of co-expressed genes involved in neuronal differentiation and cortical patterning that are either up- or down-regulated in vivo after FGF2 perturbation.