Project description:siRNAs have played a major role in cancer drug discovery, but their potential is hampered due to off-target effects. Thus, delivery systems like RNA aptamers have been used to enhance the specific delivery of these siRNAs to cancer stem cells. We report the efficacy of three different EpCAM aptamer siRNA chimeras, which were investigated both in vitro and in vivo for their ability to reduce cancer cell progression. Using these chimeras, we demonstrated specific gene knockdown in EpCAM positive cells which ultimately led to the apoptosis. To study the efficacy of these aptamer chimeras in vivo, retinoblastoma xenografts bearing NCC Rb C 51 cells were created for the first time. Systemic administration of these aptamer chimeras reduced tumour growth to about 50%. We further investigated the central Role of PLK1 in Cancer Progression and demonstrated the anti-cancer effects of targeted EpCAM siPLK1 approach. Using SILAC-Mass spectrometry analysis, we showed that silencing PLK 1 gene can lead to p53 mediated cell cycle arrest. Thus, we establish EpCAM-siRNA chimeras as potential markers for targeted anti-cancer applications, which paves a platform for efficient second line of therapies in addition to existing chemotherapy options.
Project description:Disruption of TCR /MHC class II interactions leads rapidly to alterations of the common CD4 Treg transcriptional signature Self-deprived, non-functional Tregs were compare to fully functional Tregs by microarrays. CD3ε-/- mice were lethally irradiated and their immune system reconstituted with WT mouse (WT-CD3KO chimeras) or IIKO mouse (IIKO-CD3KO) Bone Marrow cells. Twenty eight days later, peripheral Tregs from these chimeras were purified for RNA extraction and hybridization on Affymetrix microarrays.
Project description:This SuperSeries is composed of the following subset Series: GSE18588: CpG islands recruit a histone H3 lysine 36 demethylase [Illumina sequencing data] GSE21201: CpG islands recruit a histone H3 lysine 36 demethylase [Agilent data] Refer to individual Series
Project description:Sequencing of chromatin associated with H3K4me3 histone marks in live c-kit+ cells isolated by CUT&RUN from chimeras after transplantation with Ctrl-BM, MSC-BM and CpG-BM.