Project description:ETV6-RUNX1 is a fusion protein bringing together almost the entire coding sequence of RUNX1, including the DNA binding runt domain, and the N-terminus of ETV6 which is known to include transcriptional repressors including histone deacetylation 3 (HDAC3). Here we perform ChIP-seq for the active chromatin mark H3K27ac in the NALM6 B-cell acute lymphoblastic leukaemia cell line expressing ETV6-RUNX1 or mutant derivatives of ETV6-RUNX1: Delta helix-loop-helix (dHLH) is a deletion of the pointed domain; R139G is a point mutation in the runt DNA-binding domain.
Project description:Identify the expression intensity for all genes in Nalm6 cells and all the genes are divided into 4 equal groups with group 1 containing the 25% of genes that were expressed at the highest levels, and group 4 containing the 25% of genes that were expressed at the lowest levels. Total RNA are isolated from 3 lots of Nalm6 cells and gene expression are determined by microarray gene expression analysis with Nimblegen Human 385K array.
Project description:The individualized treatment of tumors has always been an urgent problem in clinical practice. Organoids-on-a-chip can reflect the heterogeneity of tumors and is a good model for in vitro anticancer drug screening. In this study, surgical specimens of patients with advanced colorectal cancer will be collected for organoid culture and organoids-on-a- chip. Use organoids-on-a-chip to screen tumor chemotherapy drugs, compare the results of patients’ actual medication regimens, and study the guiding role of organoids in the formulation of precise tumor treatment plans. The investigators will compare the response of organoids to drugs in vitro with the patient’s response to actual chemotherapy and targeted drugs and explore the feasibility and accuracy of organoids-on-a-chip based drug screening for advanced colorectal cancer. The project will establish a screening platform for chemotherapeutic drugs and targeted drugs based on colorectal cancer organoids to quickly and accurately formulate personalized treatment plans for clinical patients.
Project description:Aims:This study used cell line models and patient datasets to investigate the role of YAP1 in B- ALL. Methods: We used RNA-Seq to compare the gene expression levels of the Hippo pathway-related molecules before and after verteporfin (VP) treatment to identify important Hippo pathway-related genes in the NALM6 cell line. Results:we identified a total of 2002 differentially expressed genes in VP and DMSO treatment groups (FC ≥ 1.5, p ≤ 0.05), including 1042 upregulated and 960 downregulated genes, of which 146 were associated with the Hippo signaling pathway. Further screening resulted in 29 identified genes comprising 12 upregulated and 17 downregulated genes, which were associated with VP-treated NALM6 cells. Conclusion:Pre- and post-VP treatment, the upstream gene LATS1 was upregulated, and its overexpression increased YAP1 Ser127 site phosphorylation further studies.
Project description:Alternative splicing is a promising therapeutic target in acute lymphoblastic leukemia. Here, we report the alternative splicing changes in B-ALL cell lines including NALM6 cells and MUTZ-5 cells treated with DYRK1 inhibitor, EHT 1610 and GNF 2133. Dysregulation of co-transcriptional splicing is a therapeutic target in acute lymphoblastic leukemia (ALL). Here, we detected the alternative splicing in NALM6 cells or MUTZ-5 cells treated with EHT 1610 or GNF2133. We detected the alternative splicing in NALM6 cells cells treated with THAL-SNS-032. We also determined the alternative splicing in MEF2D-BCL9 ALL and MEF2D-HNRNPUL1 ALL patient xenografted samples treated with E7820, a anticancer sulfamide, or DMSO. Furthermore, ChIP-seq for RNA polymerase II (Pol II), p-Ser2 Pol II, and p-Ser5 Pol II were performed after DMSO or EHT 1610 treatment in NALM6 cells. ChIP-seq for p-Ser2 Pol II, and p-Ser5 Pol II were performed after DMSO or THAL-SNS-032 treatment in NALM6 cells.PRO-seq in NALM6 cells treated with DMSO, EHT 1610, and THAL-SNS-032 were performed.
