Project description:In this study we assayed for genome-wide localization of ARID3B and KDM4C enrichment in control and ARID3B-knockout OECM1 cells. The expression of the embryonic stem cell (ESC) signature in cancer cells indicates the coordinated regulation of the stemness genes in cancer stem cells, which are responsible for cancer initiation and dissemination. let-7 family microRNAs are crucial regulators for stem cell differentiation. In cancer cells, let-7 suppresses cancer stemness through targeting different oncogenes such as c-Myc, RAS, and HMGA2. However, most let-7 target genes are oncogenes rather than stemness factors, and the mechanism of let-7-repressed stemness is unclear. Here we demonstrate that let-7 supresses the formation of AT-rich interacting domain 3B (ARID3B) complex through targeting the expression of ARID3B, the interacting partner ARID3A, and importin 9. ARID3B complex recruits histone demethylase 4C (KDM4C) to the regulatory region of stemness genes for reducing histone 3 lysine 9 trimethylation, resulting in an open configuration of the chromatin of stemness genes. In cancer tissues, ARID3B expression correlates with the nuclear ARID3A expression and a worse prognosis. This result highlights the role of let-7 in regulating stemness through histone modifications.
Project description:Microarray analyses for the identification of differences in gene expression patterns have increased our understanding of the molecular mechanism of ARID3B in HNSCC.We used gene expression analysis data from FaDu-ARID3B and FaDu-pCDH to identify differentially expressed probes. The expression of the embryonic stem cell (ESC) signature in cancer cells indicates the coordinated regulation of the stemness genes in cancer stem cells, which are responsible for cancer initiation and dissemination. let-7 family microRNAs are crucial regulators for stem cell differentiation. In cancer cells, let-7 suppresses cancer stemness through targeting different oncogenes such as c-Myc, RAS, and HMGA2. However, most let-7 target genes are oncogenes rather than stemness factors, and the mechanism of let-7-repressed stemness is unclear. Here we demonstrate that let-7 supresses the formation of AT-rich interacting domain 3B (ARID3B) complex through targeting the expression of ARID3B, the interacting partner ARID3A, and importin 9. ARID3B complex recruits histone demethylase 4C (KDM4C) to the regulatory region of stemness genes for reducing histone 3 lysine 9 trimethylation, resulting in an open configuration of the chromatin of stemness genes. In cancer tissues, ARID3B expression correlates with the nuclear ARID3A expression and a worse prognosis. This result highlights the role of let-7 in regulating stemness through histone modifications.
Project description:The CLS1/CAF co-culture maintained the cancer stemness. This cancer stemness was lost when the CAF feeder cells were removed during passaging. To investigate the specific signaling pathways and markers of lung CSCs, we analyzed the gene expression profile of the CLS1 sphere after CLS1/CAF co-culture and compared this profile with that obtained for CLS1 cells cultured without feeder cells through different passages (CLS1 p3, p6, and p14) and CLF1 CLS1 sphere generated by co-culture with CAF and remove CAF to mimic cancer cell differentiation. Four time points of the CLS1 after co-culture with CAF have been collected for microarray analysis:CLS1-2 p.3, p.6, p.8, p.14. We tried to compare theCLS1 sphere-regulated gene expression profiles with the CLS1-2 p.3, p.6, p.8, p.14 and CLF1 to identify the possible cross talk mechanisms of CLF1 and CLS1 and the signaling pathways that maintain stem cell properties.