Transcriptome reprogramming through alternative splicing triggered by apigenin drives cell death in triple negative breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1013051 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Apigenin reprogrammes the transcriptome of TNBC through alternative splicing thereby exerting anti-proliferative and pro-apoptotic activities. Our findings underscore the potential impact of nutraceuticals for improved TNBC prevention and treatment.
2024-01-02 | GSE242297 | GEO
Project description:Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and resistance to cancer-specific transcriptome alterations. Alternative splicing (AS) is a major contributor to the diversification of cancer-specific transcriptomes. The TNBC transcriptome landscape is characterized by aberrantly spliced isoforms that promote tumor growth and resistance, underscoring the need to identify approaches that reprogram AS circuitry towards transcriptomes, favoring a delay in tumorigenesis or responsiveness to therapy. We have previously shown that flavonoid apigenin is associated with splicing factors, including heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2). Here, we showed that apigenin reprograms TNBC-associated AS transcriptome-wide. The AS events affected by apigenin were statistically enriched in hnRNPA2 substrates. Comparative transcriptomic analyses of human TNBC tumors and non-tumor tissues showed that apigenin can switch cancer-associated alternative spliced isoforms (ASI) to those found in non-tumor tissues. Apigenin preferentially affects the splicing of anti-apoptotic and proliferation factors, which are uniquely observed in cancer cells, but not in non-tumor cells. Apigenin switches cancer-associated aberrant ASI in vivo in TNBC xenograft mice by diminishing proliferation and increasing pro-apoptotic ASI. In accordance with these findings, apigenin increased apoptosis and reduced tumor proliferation, thereby halting TNBC growth in vivo. Our results revealed that apigenin reprograms transcriptome-wide TNBC-specific AS, thereby inducing apoptosis and hindering tumor growth. These findings underscore the impactful effects of nutraceuticals in altering cancer transcriptomes, offering new options to influence outcomes in TNBC treatments.
| S-EPMC10719380 | biostudies-literature
Project description:The changes of mature microRNA expression levels after apigenin treatment on Huh7 cells were determined. Huh7 cells were treated with 10microM apigenin for 24hr and the changes of global mature microRNA expression levels were determined.
2013-08-20 | E-GEOD-46526 | biostudies-arrayexpress
Project description:Differential gene expression in mice liver after apigenin administration. Gene expression from control mice were compared with apigenin treated mice at different dose level.
2011-04-27 | GSE12716 | GEO
Project description:Differential gene expression in mice liver after apigenin administration. Gene expression from control mice were compared with apigenin treated mice at different dose level. To study differential expression primarily at high stringency and in dose dependent manner was to increase the statistical confidence in the detection of important genes and cellular processes with a probable role in the initiation and propagation of toxicity as well as those possibly involved in regeneration during the early phase of tissue response.
2011-04-27 | E-GEOD-12716 | biostudies-arrayexpress
Project description:Apigenin regulates multiple pathways related to microvesicle biogenesis without affecting the expression of small Rho GTPase activator guanine nucleotide exchange factors (GEFs). However, apigenin can primarily targets ARHGEF1 protein, a GEF of the small GTPases, thereby inhibiting the activity of small G proteins such as Cdc42, which is essential in regulating the signaling for the release of microvesicles from tumor cells. Targeting ARHGEF1, apigenin effectively prevents tumor cells from releasing microvesicles. This, in turn, inhibits tumor angiogenesis related to VEGF90K transport on microvesicles, ultimately impeding tumor progression.
2024-07-22 | GSE251817 | GEO
Project description:Age is the primary risk factor for many chronic diseases and cognitive decline during brain aging may increase dementia risk. Hallmarks of brain aging including neuronal dysfunction and glial contribute to reduced cognitive function, and there is a persistent lack of effective treatments. Bioactive plant compounds called “nutraceuticals” can target age-related cellular processes and may protect cognitive function. Apigenin is a flavone found in plants such as chamomile and can inhibit hallmarks of aging such as cellular senescence, mitochondrial dysfunction, and impaired proteostasis. However, the underlying mechanisms of apigenin in the brain are not fully understood. Here, we characterized brain transcriptome changes in young and old mice given apigenin in drinking water and examined potential mechanisms in human astrocytes. Consistent with previous studies, we observed improved novel object recognition in old mice treated with apigenin versus old controls. Transcriptome analyses in old controls found differentially expressed genes related to immune responses, inflammation, and cytokine regulation versus young. Fewer differences were observed in old apigenin-treated versus old controls, but these changes were related to development, behavior, and antiviral responses. The majority of upregulated genes in old mice were downregulated with apigenin treatment and associated with immune responses. Similarly, the genes that were reduced with aging, but increased in old apigenin-treated mice were related to pathways important for neurological function/disease, cellular maintenance, and homeostatic signaling. We also found that glial cells drove the majority of the transcriptome differences with aging and apigenin-treatment. To explore the mechanism of action for apigenin in glial cells, we treated replicatively aged astrocytes with apigenin and observed reduced markers of inflammation and cellular senescence. Collectively, our data support the role of apigenin as a protector of cognitive and neuronal function protectant through the suppression of neuroinflammatory genes and proteins and may be especially important in non-neuronal cells.
2024-02-14 | GSE232201 | GEO
Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell cycle arrest and ultimately cell death. However, the underlying mechanisms by which co-inhibition of EGFR and ROCK induces cell death remain unclear. To investigate the synergistic effect of the combination treatment on TNBC cells, in the present study we applied a mass spectrometry-based proteomic approach to identify proteins altered upon single and combination treatments.
2019-12-04 | PXD013821 | Pride
Project description:The changes of mature microRNA expression levels after apigenin treatment on Huh7 cells were determined.
2013-08-20 | GSE46526 | GEO
Project description:To investigate the effect of apigenin on gene expression, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to suppress the cell proliferation of human acute myeloid leukemia (AML) cell lines. HL-60 amn NB4 cells were treated with apigenin for 24 h in vitro.
2022-03-31 | GSE193798 | GEO