AKR1C1 Drives Oxaliplatin Chemoresistance by Activation of STAT3 in Colorectal Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA984208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24938653.fastq.gz | Fastqsanger.gz | |||
| SRR24938654.fastq.gz | Fastqsanger.gz | |||
| SRR24938655.fastq.gz | Fastqsanger.gz | |||
| SRR24938656.fastq.gz | Fastqsanger.gz | |||
| SRR24938657.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:AKR1C1, a member of the AKR1C family, has been identified as a key player in cancer progression, promoting cancer cell proliferation and inhibiting apoptosis. Here, we identified AKR1C1 as a potential crucial gene significantly associated with oxaliplatin (OXA) sensitivity and unfavorable clinical outcomes through the transcriptome analysis of OXA-sensitive and -resistant colorectal cancer cell lines. Both in vitro and in vivo, AKR1C1 promotes cancer cell proliferation and confers OXA chemoresistance in colorectal cancer cells. Mechanistically, AKR1C1 interacts with and activates STAT3 and increases glutathione (GSH) levels, resulting in chemoresistance in colorectal cancer cells. Moreover, pharmacologic inhibition of AKR1C1 with alantolactone restores the sensitivity of resistant cell lines to OXA and the combined treatment of alantolactone with OXA exhibits superior antitumor effects in mouse xenografts. Collectively, the present study offers compelling evidence that AKR1C1 expression confers resistance to OXA in colorectal cancer, providing a promising strategy to circumvent chemoresistance.
2024-12-11 | GSE235026 | GEO
Project description:Almost half of the patients with advanced colorectal cancer (CRC) are resistant to oxaliplatin based therapy, the first line treatment for CRC. Therefore, predicting and understanding oxaliplatin resistance is important to improve CRC patient survival. Investigated here is the use of proteomic folding stability measurements to differentiate oxaliplatin resistant and sensitive CRCs using patient-derived CRC cell lines and patient-derived xenografts (PDXs). Three protein stability profiling techniques (including the Stability of Proteins from Rates of Oxidation (SPROX), the Thermal Protein Profiling (TPP), and Limited Proteolysis (LiP) approaches) were employed to identify differentially stabilized proteins in 6 patient-derived CRC cell lines with different oxaliplatin sensitivities and 8 CRC PDXs derived from 2 of the patient derived cell lines with different oxaliplatin sensitivity. A total of 23 proteins were found in at least 2 techniques to be differentially stabilized in both the cell line and PDX studies of oxaliplatin resistance. These 23 differentially stabilized proteins included 9 proteins that have been previously connected to cancer chemoresistance. Over-representation analysis (ORA) of all the differentially stabilized proteins identified here, revealed novel pathways related to oxaliplatin resistance. Compared to conventional protein expression level analyses, which were also performed on the cell lines and PDXs, the stability profiling techniques identified novel proteins and pathways and provided new insight on the molecular basis of oxaliplatin resistance. Our results suggest that protein stability profiling techniques are complementary to expression level analyses for identifying biomarkers and understanding molecular mechanisms associated with oxaliplatin chemoresistance in CRC and disease phenotypes in general.
2023-04-28 | PXD036298 | Pride
Project description:Resistance to chemotherapy drugs, including oxaliplatin, remains a major challenge in the treatment of colorectal cancer, often leading to treatment failure and poor patient outcomes. Overcoming chemoresistance by sensitizing tumor cells represents a critical therapeutic goal. Adenoviral early region 1A (E1A) has been proposed as a promising gene therapy agent capable of modulating cellular pathways to enhance sensitivity to chemotherapeutic agents. This dataset contains RNA-seq profiling of human colorectal cancer cell lines that are either oxaliplatin-sensitive (HCT116) or oxaliplatin-resistant (HCT116 oxpl-R), treated with oxaliplatin, in the context of doxycycline-induced adenoviral E1A expression. The experiment includes eight conditions: untreated controls, E1A expression alone, oxaliplatin treatment alone, and combined E1A expression with oxaliplatin treatment, each in both sensitive and resistant cell lines. The comprehensive experimental design enables the dataset to be divided into three independent analyses: A) Comparison of baseline transcriptomic profiles between oxaliplatin-sensitive and resistant cells (conditions 1 and 5); B) Investigation of the transcriptional response to oxaliplatin in sensitive and resistant cells (conditions 1, 3, 5, and 7); C) Evaluation of the impact of adenoviral E1A expression on the transcriptomes of sensitive and resistant cells alone (conditions 1, 2, 5, and 6) and in combination with oxaliplatin treatment (all eight conditions); This dataset provides valuable insights into the molecular mechanisms underlying oxaliplatin resistance and the potential role of E1A gene therapy in sensitizing colorectal cancer cells to chemotherapy.
2025-11-14 | GSE304295 | GEO
Project description:Colorectal cancer (CRC) is one of the most common malignancies worldwide. Oxaliplatin chemoresistance is a major challenge in the clinical treatment of CRC. Through bioinformatics analysis, we identified WDR43 as a critical potential oncogenic factor in CRC pathogenesis. Clinically, WDR43 is highly expressed in CRC, and WDR43 overexpression is associated with poor prognosis in CRC patients. WDR43 knockdown significantly inhibits cell growth by arresting the cell cycle and enhances the effect of oxaliplatin chemotherapy capacities in vitro and in vivo. Mechanistically, upon oxaliplatin stimulation, c-MYC promotes the transcriptional regulation and expression of WDR43. WDR43 enhances the ubiquitination of p53 by MDM2 by binding RPL11, thereby reducing the stability of the p53 protein, which further induces the proliferation and chemoresistance of CRC cells. Thus, WDR43 may not only mark CRC progression but also be a potential therapeutic target of chemoresistance in CRC.
2025-07-01 | GSE207378 | GEO
Project description:Oxaliplatin resistance frequently leads to therapeutic failure in colorectal cancer (CRC). Increasing evidence has shown that noncoding RNAs (ncRNAs) play pivotal roles in chemoresistance of CRC. However, the roles and mechanisms of ncRNAs in oxaliplatin resistance are not well understood. In this study, to identify the ncRNAs induced by oxaliplatin, we profile the expression of ncRNAs in oxaliplatin-resistant HCT116 CRC cells (HCT116oxR) and parental HCT116 cells using next-generation sequencing technology.
2023-08-31 | GSE119603 | GEO
Project description:In the present study, we investigated miRNA expression changes caused by aquired chemoresistance to 5-FU or Oxa. 40 and 14 miRNAs were detected as differentially expressed in 5-fluouracil- and oxaliplatin-resistant colorectal HCT116 sublines, respectively. Differentially expressed miRNAs determined in the present study could be applied for further development of diagnostic and therapeutic applications for colorectal cancer carcinoma resistant to 5-FU or Oxa.
2019-12-31 | GSE119481 | GEO
Project description:PHGDH Drives 5-FU Chemoresistance in Colorectal Cancer through the Hedgehog signaling
| PRJNA1251002 | ENA
Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer. Fourty-two human tumors and murine explants of colorectal origin, both primary colon and of various metastatic sites, were processed for total RNA. The samples included RNA from 14 patient samples in addition to RNA from Patient-Derived Colorectal Cancer Explant (PDCCEs) generated from these 14 patient samples. The PDCCEs were processed as fresh frozen whole tumor in addition to formalin-fixed paraffin-embedded (FFPE) tumors.
2012-02-17 | E-GEOD-28691 | biostudies-arrayexpress
Project description:Oxaliplatin resistance was induced in 2 colorectal cancer cell lines (LoVo-92, wt-p53 and LoVo-Li, functionally inactive p53) and one ovarian cancer cell line (A2780, wt-p53). Resistance was induced by weekly exposure to oxaliplatin for 4 hrs or 72 hrs with increasing concentrations for a period of 7 months Genomic DNA of oxaliplatin and cisplatin resistant colorectal cancer and ovarian cancer cell lines as well as the parental cell lines were labeled and subsequently hybridized against pooled reference DNA of healthy volunteers of the opposite gender using across array hybridization. Extracted raw-data were normalised and smoothend using the R-script NOWAVE resulting in normalised log2 ratio profiles of resistant cell line versus parental cell line and parental cell line versus reference DNA.
2014-03-01 | E-GEOD-20144 | biostudies-arrayexpress
Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer.
2012-02-17 | GSE28691 | GEO