NRF2 signalling associated with radioresistance in colorectal cancer models
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136011 | GEO | 2021/08/03
REPOSITORIES: GEO
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Project description:NRF2 signalling associated with radioresistance in colorectal cancer models
| PRJNA560938 | ENA
Project description:To explore the mechanisms underlying the radioresistance of colorectal cancer, we established specifically radioresistant HCT116 cell line (HCT116-R cells) and RKO cell line (RKO-R cells) derived from HCT116 and RKO cell lines by repeatedly exposing to multi-fractionated irradiation. Then, the aberrantly expressed miRNA were detected by miRNA sequencing and their bioinformatics were analyzed.
2021-01-10 | GSE159528 | GEO
Project description:Purpose: Alterations in the KEAP1/NFE2L2 (NRF2)/CUL3 pathway occur in ~20% of human head and neck squamous cell carcinomas (HNSCC) and are associated with resistance to standard-of-care therapy. However, this pathway's role in radiotherapy resistance in HNSCC has not been well-studied. Experimental Design: We generated genetically engineered mouse models and developed primary murine cancer cell lines harboring mutations commonly observed in human HNSCC, including inducible activation of PIK3CA and deletion of Trp53, with or without Keap1 loss. Primary tumors were initiated via 4-hydroxytamoxifen injection ± the tobacco carcinogen benzo[a]pyrene (BAP) into the oral buccal mucosa. Tumors were analyzed using Western blotting, immunohistochemistry, RNA sequencing (RNA-seq), and subjected to fractionated radiation therapy to investigate the role of the KEAP1/NRF2 pathway in radioresistance and modulation of the tumor immune microenvironment. Results: BAP exposure accelerated primary tumor formation within one month, with histological analysis confirming invasive squamous cell carcinoma, validated by cytokeratin and differentiation marker expression. Primary cell lines derived from Keap1-haploinsufficient tumors exhibited upregulation of NRF2 target genes and a radioresistant phenotype, which was reversed post-Nrf2 knockdown in vitro. Bulk RNA-seq revealed that Keap1 haploinsufficiency correlated with NRF2 pathway activation, increased myeloid infiltration, and enhanced angiogenic signatures. In vivo, Keap1 haploinsufficiency promoted accelerated tumor growth and decreased survival. Finally, using fractionated radiotherapy, we showed that Keap1 haploinsufficient primary tumors were significantly more radioresistant than Keap1-proficient tumors, regardless of BAP exposure. Conclusion: These data demonstrate that Keap1 haploinsufficiency in HNSCC is linked to unfavorable tumor immune microenvironment, aggressive growth, and a radioresistant phenotype.
2025-07-08 | GSE301971 | GEO
Project description:WGS and RNA-seq data for Nrf2 study
| EGAS00001001740 | EGA
Project description:The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors the activity of Nrf2 is inhibited by its interaction with the kelch-like ECH-associated protein 1 (Keap1). Here, we describe RA839, a small molecule that binds non-covalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of approximately 6 µM, as demonstrated by X-ray co-crystallization and isothermal titration calorimetry. Whole-genome DNA arrays showed that at 10 µM RA839 significantly regulated 105 genes in bone marrow-derived macrophages. Canonical pathway mapping of these genes revealed an activation of pathways linked with Nrf2 signalling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knockout macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound CDDO-Me, RA839 prevented the induction of both inducible nitric oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice RA839 acutely induced Nrf2-target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2. Gene expression profile of bone marrow derived murine macrophages (BMDM) from Nrf2+/+ or Nrf2-/- mice treated with RA838, siKeap1-1 or siKeap1-2 were compared to untreated DMSO control or siControl. Four biological replicates were used for each sample group.
2015-10-31 | E-GEOD-71695 | biostudies-arrayexpress
Project description:Colorectal cancer is known as one of the most common cancer and the third leading cause of death worldwide. Nrf2 is considered as a main transcription factor for producing antioxidants in response to oxidative stress and reduce damages to the cell. It also plays a crucial role in drug resistance. In this study, the Nrf2 gene was knocked down in HT-29 cell line and then the protein expression profile were investigated by TMT based LC MS/MS approach.
2022-05-04 | PXD027360 | Pride
Project description:Transcriptional profiling of hPTTG1-/- HCT116 human colorectal cancer cells comparing hPTTG1-/- HCT116 cells transfected with pcDNA3.1, and with hPTTG1-/- HCT116 cells transfected with pcDNA3.1-hPTTG1 plasmid.
2014-01-02 | GSE26434 | GEO
Project description:Six non- and drug-resistant colorectal cancer cell lines were selected in this study, which were non-resistant cell lines: HCT116 and LoVo, four drug-resistant cell lines: HCT116-OxPt, HCT116-SN38, LoVo-OxPt, LoVo-SN38.Proteins extraced from three HCT116 related cell lines were labled and pooled together, and proteins from other three LoVo related cell lines were labled and pooled together.
2022-03-04 | PXD004070 | Pride
Project description:Cancer stem cells (CSCs) are present in small quantities in tumor populations. To permit various analyses of CSCs, we attempted to enrich and expand ornithine decarboxylase (ODC) degron-transduced colorectal cancer (CRC) cells, which retain low proteasome activity. ZsGreen fluorescence-positive (ZsGreen+) cells were collected by sorting the ODC degron-transduced HCT116, DLD1, and SW480 cells, which were defined as enriched ZsGreen+ cells. ZsGreen+ cells still maintained CSC properties. These cells had higher stem cell marker expression and increased resistance to chemotherapy with 5-fluorouracil and oxaliplatin. ZsGreen+ HCT116 and DLD1 cells had greater sphere-forming ability and enhanced tumorigenicity compared to ZsGreen- control cells. Time-lapse microscopy showed that a single enriched ZsGreen+ HCT116 cell had asymmetric cell division. Thus, model CSCs were acquired in sufficient quantity. Using these cells, we performed a comprehensive microRNA analysis; miR- 491-3p was a candidate to suppress cancer stemness. Finally, we found that up- regulated genes in the enriched HCT116 ZsGreen+ cells correlated with those up- regulated in human clinical spheroid samples established from patient-derived xenografts derived from CRC tissue samples, further supporting the acquisition of enriched model CSCs. These cells would be useful in identifying novel CSC markers and developing medicine for anti-CSC therapy.
2025-07-09 | GSE282048 | GEO
Project description:Transcriptional profiling of hPTTG1-/- HCT116 human colorectal cancer cells comparing hPTTG1-/- HCT116 cells transfected with pcDNA3.1, and with hPTTG1-/- HCT116 cells transfected with pcDNA3.1-hPTTG1 plasmid. Two-condition experiment, pchyg vs. 7-2 and 18-2 cells. 1 control, 2 different transfected cells.
2014-01-02 | E-GEOD-26434 | biostudies-arrayexpress