characteristics.text: SAMN41726409
characteristics.characteristic: External Id
characteristics.text: Incheon National University
characteristics.characteristic: INSDC center name
characteristics.text: 2024-06-07T00:00:00Z
characteristics.characteristic: INSDC first public
characteristics.text: 2024-06-07T05:01:10.013Z
characteristics.characteristic: INSDC last update
characteristics.text: live
characteristics.characteristic: INSDC status
characteristics.text: Human
characteristics.characteristic: NCBI submission model
characteristics.text: Human.1.0
characteristics.characteristic: NCBI submission package
characteristics.text: ERS23033711
characteristics.characteristic: SRA accession
characteristics.text: 69
characteristics.characteristic: age
characteristics.text: the lab of Professor Jeongwon Sohn at the Korea University College of Medicine, located at 73 Inchon-ro, Seongbuk-gu, Seoul, Republic of Korea.
characteristics.characteristic: biomaterial_provider
characteristics.text: MCF-7 cell line
characteristics.characteristic: cell_line
characteristics.text: 2021-06-17
characteristics.characteristic: collection_date
characteristics.text: Back ground The transcriptomic profile of cellular senescence is strongly associated with distinct cell types, the specific stressors triggering senescence, and temporal progression through senescence stages. This implies the potential necessity of conducting separate investigations for each cell type and a stressor inducing senescence. To elucidate the molecular mechanism that drives endoplasmic reticulum (ER) stress-induced cellular senescence in MCF-7 breast cancer cells, with a particular emphasis on the ATF6a branch of the unfolded protein response. We conducted transcriptomic analysis on MCF-7 cells by ectopic expression of ATF6a. Methods Transcriptomic sequencing was conducted on MCF-7 cells at 6 and 9 hours post senescence induction through ATF6a ectopic expression. Comprehensive analyses encompassing enriched functional annotation, canonical pathway analysis, gene network analysis, upstream regulator analysis and gene set enrichment analysis were performed on Differentially Expressed Genes (DEGs) at 6 and 9 hours as well as timerelated DEGs. Regulators and their targets identified from the upstream regulator analysis were validated through RNA interference, and their impact on cellular senescence was assessed by senescence-associated b-galactosidase staining. Results ATF6a ectopic expression resulted in the identification of 12 and 79 DEGs at 6 and 9 hours, respectively, employing criteria of a false discovery rate < 0.05 and a lower fold change (FC) cutoff |log2FC| > 1. Various analyses highlighted the involvement of the UPR and/or ER Stress Pathway. Upstream regulator analysis of 9 hour-DEGs identified six regulators and eleven target genes associated with processes related to cytostasis and 'cell viability and cell death of connective tissue cells.' Validation confirmed the significance of MAP2K1/2, GPAT4, and PDGF-BB among the regulators and DDIT3, PPP1R15A, and IL6 among the targets. Conclusion Transcriptomic analyses and validation reveal the importance of the MAP2K1/2/GPAT4-DDIT3 pathway in driving cellular senescence following ATF6a ectopic expression in MCF-7 cells. This study contributes to our understanding of the initial molecular events underlying ER stress-induced cellular senescence in breast cancer cells, providing a foundation for exploring cell type- and stressor-specific responses in cellular senescence induction.
characteristics.characteristic: description
characteristics.text: USA
characteristics.characteristic: geo_loc_name
characteristics.text: The MCF-7 cell line was derived from a 69-year-old Caucasian female breast cancer patient's pleural effusion.
characteristics.characteristic: isolate
characteristics.text: Homo sapiens
characteristics.ontologyTerms: http://purl.obolibrary.org/obo/NCBITaxon_9606
characteristics.characteristic: organism
characteristics.text: female
characteristics.characteristic: sex
characteristics.text: breast cancer
characteristics.characteristic: tissue
characteristics.text: RNA sequencing of ATF6a-induced cellular senescence in MCF-7 cell line
characteristics.characteristic: title