Project description:We identifled FOSL1 and HDAC2 as master regulators of cancer cell metabolism. To validate their function, we knockdown FOSL1 in pancreatic adenocarcinoma cell line PANC-1 and HDAC2 in lung adenocarcinoma cell line H1299, respectively. Then RNA-seq was performed to investigate the alterations of metabolic genes.
Project description:Determine the effect and specificity of HDAC2 siRNA compared to SAHA inhibition of HDAC2 in hepatocellular carcinoma (HCC) Profile of treated cells compared to control Transcriptomic profiling
Project description:To explore genome-wide alteration MED1 and FOSL1 after depletion of FOSL1, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of SCC1 cells to examine genome-wide recruitment of MED1 and FOSL1 following FOSL1 knockdown. Depletion of FOSL1 led to dramatically loss of the recruitment of MED1 and FOSL1 at a cohort of key oncogenes associate with tumorigenesis and metastasis.
Project description:Background Epigenetic mutations are involved in oncogenesis and therefore their regulator Histone deacetylaces (HDACs) can be a therapeutic target. In this study, we investigated the anticancer effect and mechanism of pan-HDAC inhibitor, LBH589, against undifferentiated pleomorphic sarcoma (UPS). Method To elucidate the molecular target, we performed RNA microarray for UPS cells after treated LBH589. Data were validated by RT-PCR and Westernblot. Result We found that LBH589 decrease the expression of Fos-like 1 (FOSL1) gene in four UPS cell lines. Knockdown of FOSL1 by RNA interference inhibited cell proliferation and conversely, overexpression increased cell proliferative capacity. Furthermore, we showed that knockdown of FOSL1 cause elevation of p21 expression in UPS cells. Conclusion FOSL1 codes the FRA-1 protein and forms activator protein-1 (AP-1) complexes in collaboration with members of the JUN family to drive gene transcription. FOSL1 is overexpressed in several malignant tumors and considered to be a poor prognostic factor. In this study, we showed that the antitumor effect by HDAC inhibitor is partly due to down regulation of FOSL1.
Project description:A subset of human pancreatic ductal adenocarcinoma cells (PDACs) is characterized by high Fosl1 expression and Fosl1 is linked to the control of pro-inflammatory pathways and growth of PDAC cells. To mimick the human disease in mice (> 90% of PDAC patients harbour Kras mutations) the mutated LSL-KrasG12D allele was combined with the pancreas specific Cre recombinase Ptf1aCre (p48Cre). The two pancreatic cancer cell lines (Ptf1aCre, LSL-KrasG12D/+) were isolated from these mice and used for transcriptomics studies. The two different murine pancreatic cancer cell lines (Ptf1aCre, LSL-KrasG12D) were treated with two different Fosl1 siRNAs and one control siRNA, each. 72h after transfection a sufficient knockdown was tested by immunoblotting and qPCR. Total mRNA was isolated and checked for integrity. According to manufacture's recommendation the samples were subjected to microarray analysis using the Affymetrix Mouse Gene ST 1.0 array chip to discover differentially expressed genes.
Project description:In hemochorial placentation, trophoblast stem cells differentiate into multiple lineages to aquire specific functions, such as invasive and endocrine phenotype. FOSL1 has been identified as a key regulator for trophoblast differentiation. We used microarray to detail mechanisms underlying FOSL1 signaling pathway in trophoblast differentiation. 3 replicates of differentiated Rcho1 TS cells expressing control shRNA; 3 replicates of differentiated Rcho1 TS cells expressing Fosl1 shRNA
Project description:Transcriptome analysis of prostate cancer patient derived organoid MKS-PCa3 upon knockdown of FOSL1, YAP, TAZ, or YAP/TAZ mediated by siRNAs
Project description:Despite recent advances in genomic profiling techniques, the precise mechanisms controlling GBM subtypes and their plasticity are not fully unraveled. Here,using transcriptomic data of patient derived stem cell lines we found that FOSL1 is a master regulator of the MES subtype. Depletion of FOSL1 resulted in loss of themesenchymal gene signature (MGS) in mouse Kras-mutant neural stem cells and in human brain tumor stem cells.