ArticlePloS one2024
Transcriptomic analysis of cellular senescence induced by ectopic expression of ATF6α in human breast cancer cells.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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 ATF6α branch of the unfolded protein response. We conducted transcriptomic analysis on MCF-7 cells by ectopic expression of ATF6α.
methodsTranscriptomic sequencing was conducted on MCF-7 cells at 6 and 9 hours post senescence induction through ATF6α 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 time-related 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 β-galactosidase staining.
resultsATF6α 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.
conclusionTranscriptomic analyses and validation reveal the importance of the MAP2K1/2/GPAT4-DDIT3 pathway in driving cellular senescence following ATF6α 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.