Project description:Transcriptional profiling of cisplatin sensitive NPCs 6-condition experiment, CNE2 vs. S16 cells at 0, 2 or 8 hr treatment. Biological replicates: 2 for each control (0 hr), 2 for each treatment (2 hr and 8 hr), independently grown and harvested, dye-swapped.
Project description:Genomic analyses of SCC have yet to yield significant strategies against pathway activation to improve treatment. Platinum-based chemotherapy remains the mainstay of treatment for SCC of different histotypes either as a single agent or alongside other chemotherapeutic drugs or radiotherapy; however, resistance inevitably emerges, which limits the duration of treatment response. To elucidate mechanisms that mediate resistance to cisplatin, we compared drug-induced perturbations to gene expression between cisplatin-sensitive and -resistant SCC cells. Cisplatin-sensitive and -resistant SCC cells were identified through MTS assay. Gene expression profiling (Affymetrix GeneChip 1.0ST) was performed to identify putative genes and cellular pathways that may be associated with cellular response to cisplatin.
Project description:The development of therapeutic resistance and metastatic dissemination takes place in 20-30% patients with nasopharyngeal carcinoma (NPC), resulting in poor survival. Hence, a better understanding of the underlying molecular mechanisms will help improve clinical outcome. We have identified a novel circRNA, circIPO7, as a promoter of metastasis and cisplatin chemoresistance in NPC cells. Expression profiling and Genome binding/occupancy profiling by high throughput sequencing were performed to explore the underlying molecular mechanisms.
Project description:The development of therapeutic resistance and metastatic dissemination takes place in 20-30% patients with nasopharyngeal carcinoma (NPC), resulting in poor survival. Hence, a better understanding of the underlying molecular mechanisms will help improve clinical outcome. We have identified a novel circRNA, circIPO7, as a promoter of metastasis and cisplatin chemoresistance in NPC cells. circIPO7 was found to bind to YBX1. Genome binding/occupancy profiling by high throughput sequencing were performed to explore the underlying molecular mechanisms.
Project description:This SuperSeries is composed of the following subset Series: GSE15372: Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. GSE15373: Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. Refer to individual Series
Project description:Platinum-based chemotherapeutics are used in many combination regimens in cancer. Despite extensive use across diverse cancer types, there is room for improved efficacy and patient selection for treatment. Here, we use bladder cancer to address both issues. A multi-omic assessment of five human bladder cancer cell lines and their chemotherapy resistant derivatives, coupled with in vitro whole-genome CRISPR screens were used to define functional drivers of treatment resistance. We identified 46 genes that sensitized the resistant cell lines to cisplatin plus gemcitabine (GemCis), a standard combination therapy in bladder cancer. Most genes were involved with DNA damage and repair pathways, which have previously been associated with enhanced sensitivity to cisplatin. Evaluating expression of the 46 genes in the whole transcriptome and proteome data in parental and resistant lines identified the puromycin sensitive aminopeptidase, NPEPPS, as a novel hit. Depletion of NPEPPS resulted in sensitizing resistant bladder cancer cells to cisplatin in vitro and in xenograft experiments. Pharmacologic inhibition of NPEPPS with tosedostat in cells and in chemoresistant, bladder cancer patient-derived tumoroids improved response to cisplatin. Prior work found NPEPPS in a protein complex with volume regulated anion channels (VRACs) in several cell line models. Interestingly, depletion of two VRAC subunits, LRRC8A and LRRC8D, known importers of intracellular cisplatin, enhanced resistance to cisplatin. Our findings support NPEPPS as a novel and druggable driver of cisplatin resistance with the potential for rapid translation to clinical investigation.
Project description:Platinum-based chemotherapeutics are used in many combination regimens in cancer. Despite extensive use across diverse cancer types, there is room for improved efficacy and patient selection for treatment. Here, we use bladder cancer to address both issues. A multi-omic assessment of five human bladder cancer cell lines and their chemotherapy resistant derivatives, coupled with in vitro whole-genome CRISPR screens were used to define functional drivers of treatment resistance. We identified 46 genes that sensitized the resistant cell lines to cisplatin plus gemcitabine (GemCis), a standard combination therapy in bladder cancer. Most genes were involved with DNA damage and repair pathways, which have previously been associated with enhanced sensitivity to cisplatin. Evaluating expression of the 46 genes in the whole transcriptome and proteome data in parental and resistant lines identified the puromycin sensitive aminopeptidase, NPEPPS, as a novel hit. Depletion of NPEPPS resulted in sensitizing resistant bladder cancer cells to cisplatin in vitro and in xenograft experiments. Pharmacologic inhibition of NPEPPS with tosedostat in cells and in chemoresistant, bladder cancer patient-derived tumoroids improved response to cisplatin. Prior work found NPEPPS in a protein complex with volume regulated anion channels (VRACs) in several cell line models. Interestingly, depletion of two VRAC subunits, LRRC8A and LRRC8D, known importers of intracellular cisplatin, enhanced resistance to cisplatin. Our findings support NPEPPS as a novel and druggable driver of cisplatin resistance with the potential for rapid translation to clinical investigation.
Project description:Platinum resistance is a major drawback in the treatment of ovarian cancer. Evidence suggests that microRNAs are key players in the initiation, progression, and drug resistance of cancer cells. However, the precise miRNAs dysregulated and contributing to platinum resistance in ovarian cancer cells have not been fully elucidated. Here, we conducted a miRNA expression profiling of cisplatin-sensitive (A2780) and cisplatin-resistant (CP20 and CIS) ovarian cancer cells to identify potential miRNAs involved in platinum resistance.