Dataset Information

Effect of adenoviral E1A on oxaliplatin response in oxaliplatin-sensitive and resistant human colorectal cancer HCT116 cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304295 | GEO | 2025/11/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Purpose: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. Methods: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38- or oxaliplatin-resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of DNA methylation entropy to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. Results: We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences -- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy. Investigation of the representive methylome of well-established SN38 and Oxaliplatin resistant cell line models and 14 clinical colorectal metastatic samples that have developed resistance to XELOX to review the epigenetic mechnism of the drug resistance.

Dataset Information

Effect of adenoviral E1A on oxaliplatin response in oxaliplatin-sensitive and resistant human colorectal cancer HCT116 cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets