Project description:In our previous study, the roles of heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) in CML cells were revealed. We found that overexpression of HNRPDL transformed murine BaF3 cells and induced lethal mice leukemia. Conversely, HNRPDL silencing inhibited colony-forming cell (CFC) production of CML CD34+ cells and attenuated BCR-ABL induced mice leukemia. In addition, HNRPDL modulated imatinib response of K562 cells and HNRPDL silencing sensitized CML CD34+ cells to imatinib treatment. To obtain molecular insights of how HNRPDL modulates the growth and imatinib response of human CML cells, we generated microarray data comparing HNRPDL silenced K562 cells with control (Scramble) cells.
Project description:We have completed the mRNA expression profiling of human granulosa-like tumor cell line KGN to reveal the differentially expressed mRNAs upon lncRNA DDGC knockdown.
Project description:A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. Two cell lines are compared, which are K562 erythroblastic leukemia cells sensitive to methotrexate and K562 cells resistant to 10e-5M methotrexate. Six samples are provided which correspond to triplicates of each cell line. The samples provided were analyzed using the specific software GeneSpring GX.