RRBP1 rewires Cisplatin resistance in Oral Squamous Cell Carcinoma by regulating YAP-1
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PROVIDER: PRJEB40913 | ENA |
REPOSITORIES: ENA
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Project description:The RNA-seq library preparation was performed on H357 CisS at 0 month,H357 CisR at 4 months, and H357 CisR at 8 months whereas CisR represent Cisplatin drug resistance and CisS denote sensitive to Cisplatin. Additional, we also performed gene specific knockdown on H357CisR 8 months RRPB1 Sh. In experiment, We have added two independent biological replicates of each samples to understand the role of causative factor for cisplatin resistance at transcriptomic level. Total RNA isolated from above mentions experiment and 2 μg of RNA was used to prepared library. The mRNA was isolated through magnetic beads using mRNA isolation kit (PolyA mRNA isolation Module, NEB) followed by RNA-seq library preparation using mRNA library preparation kit (NEB) strictly following the vendor recommended protocol. After library preparation concentration of libraries was estimated using qubit 2.0 (Invitrogen) and the recommended fragmentation sizes were confirmed by Tapestation (Agilent).
2020-12-31 | E-MTAB-9697 | biostudies-arrayexpress
Project description:Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (YAP/TAZ) in human SCC2 oral cancer cells. Human SCC2 oral cancer cells were transfected with control siRNA, or siRNAs targeting TAZ, YAP, or YAP/TAZ for 48 hours. Total RNA from three independent experiments carried out on separate days was isolated and purified and the samples were then profiled on Affymetrix Human Gene 2.0 Chips at the Boston University Microarray Core. The expression profiles were processed and normalized using the Robust Multi-array Average (RMA) procedure (23) based on a custom Brainarray CDF (24). For each of the siRNA experiments, signatures of genes differentially expressed between treatment and corresponding siRNA control with an FDR q-value ?0.05 and a fold change ?2 were identified as either activated (up-regulated in control) or repressed (up-regulated in treatment). The overlap between the differentially expressed gene signatures was evaluated by Fisher test. Hierarchical gene and sample clustering was performed on the top 3000 genes with highest median absolute deviation (MAD; a robust version of the variance) across 12 samples, using “ward” as the agglomeration rule, and 1 minus Pearson correlation and Euclidean as the distance measures for genes and samples, respectively.
2015-05-26 | E-GEOD-66949 | biostudies-arrayexpress
Project description:Identification of CMTM6 as a novel mediator of cisplatin resistance in oral squamous cell carcinoma
2020-01-07 | MSV000084761 | MassIVE
Project description:Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (YAP/TAZ) in human SCC2 oral cancer cells.
2015-05-26 | GSE66949 | GEO
Project description:The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established We used microarrays to assess the role of YAP pathway in cholangiocarcinoma either by overexpressing a constitutively active YAP1 mutant, or by downregulating YAP1 expression using shRNA HuCCT1 cells where transfected with either an empty vector or a vector overexpressing the constitutively active YAP1 S127A; cells were harvested, RNA was collected and analyzed using microarray
2015-10-27 | E-GEOD-61764 | biostudies-arrayexpress
Project description:The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established We used microarrays to assess the role of YAP pathway in cholangiocarcinoma either by overexpressing a constitutively active YAP1 mutant, or by downregulating YAP1 expression using shRNA HuCCT1 cells where transfected with either a control scrambled shRNA or a shRNA targeting YAP1; cells were harvested, RNA was collected and analyzed using microarray
2015-10-27 | E-GEOD-61765 | biostudies-arrayexpress
Project description:Cisplatin is a commonly used platinum-based chemotherapeutic agent for oral squamous cell carcinoma (OSCC). However, cisplatin efficacy is limited by drug toxicity and the resistance capabilities of cancer cells. Reduced efficacy of anticancer therapy has been recently attributed to the presence of therapy-insensitive subpopulations in heterogeneous tumours, known as cancer stem-like cells (CSCs). CSCs comprise a tumour-forming subpopulation of cells that exhibit stem cell-like features, including the abilities to self-renew and turn into progenitor and differentiated cancer cell lineages, and enhanced therapeutic resistance capabilities, thus driving the continual growth and survival of tumours. Overall, this work was conducted to provide the transcriptomes of the OSCC cell lines with differing responses to cisplatin using a microarray analysis. The data may be analyzed alongside other similar datasets to explore the underlying cisplatin resistance mechanisms in OSCC.
2021-03-09 | GSE168424 | GEO
Project description:chemoresistance frequently leads to therapeutic failure in oral squamous cell carcinoma (OSCC). Recently, studies have reported that lncRNAs play active roles in regulation biological properties of cancer. To understand whether lncRNAs involve in regulating cisplatin sensitivity in TSCC, in this study, we profiled the expression of lncRNAs in two TSCC cell lines(CAL-27 and SCC-9) under cisplatin treatment paired untreated cell lines by LncRNA Array (ArrayStar V3.0).
2018-06-12 | GSE114929 | GEO
Project description:CMTM6 drives cisplatin resistance by regulating AKT mediated Wnt signaling
| PRJEB39795 | ENA
Project description:YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes. PUBLICATION ABSTRACT:; The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Experiment Overall Design: MCF10A cells were infected with retrovirus constructs (vector or YAP) and puromycin was used to select for transduced cells. Cells were split and grown to ~60-75%% confluency at which point they were harvested for RNA. Vector vs. YAP comparison was done in duplicate.
2008-06-11 | E-GEOD-10196 | biostudies-arrayexpress