Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA688896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13337075.fastq.gz | Fastqsanger.gz | |||
| SRR13444945_1.fastq.gz | Fastqsanger.gz | |||
| SRR13444945_2.fastq.gz | Fastqsanger.gz | |||
| SRR13444946_1.fastq.gz | Fastqsanger.gz | |||
| SRR13444946_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:Up-regulation of the neuropeptide NTS in a subgroup of lung cancers has been linked to poor prognosis. However, the regulatory pathway centered on NTS in lung cancer remains unclear. Here we identified the NTS specific enhancer in lung adenocarcinoma cells. The AF4/FMR2 (AFF) family protein AFF1 occupies the NTS enhancer and inhibits NTS transcription. Clustering analysis of lung adenocarcinoma gene expression data demonstrated that NTS is highly positively correlated with the expression of the oncogenic factor CPS1. Detailed analyses demonstrated that NTS antagonizes the IL6 pathway in regulating CPS1. Thus, our analyses revealed a novel NTS centered regulatory axis, consisting of AFF1 as a master transcription suppressor and IL6 as an antagonist in lung adenocarcinoma cells.
2021-03-23 | GSE164098 | GEO
Project description:Upregulation of the neuropeptide neurotensin (NTS) in a subgroup of lung cancers has been linked to poor prognosis. However, the regulatory pathway centered on NTS in lung cancer remains unclear. Here we identified the NTS-specific enhancer in lung adenocarcinoma cells. The AF4/FMR2 (AFF) family protein AFF1 occupies the NTS enhancer and inhibits NTS transcription. Clustering analysis of lung adenocarcinoma gene expression data demonstrated that NTS expression is highly positively correlated with the expression of the oncogenic factor CPS1. Detailed analyses demonstrated that the IL6 pathway antagonizes NTS in regulating CPS1. Thus, our analyses revealed a novel NTS-centered regulatory axis, consisting of AFF1 as a master transcription suppressor and IL6 as an antagonist in lung adenocarcinoma cells.
| S-EPMC7949158 | biostudies-literature
Project description:Gene expression alterations induced by recombinant CPS1 in hepatic macrophages of mice with acetaminophen-induced liver injury
2019-03-26 | GSE122879 | GEO
Project description:Auxin critically regulates nearly every aspect of plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. Although ARF protein stability is regulated via the 26S proteasome, molecular mechanisms underlying ARF stability and turnover are unknown. Here, we report the identification and functional characterization of an F-Box E3 ubiquitin ligase, which we have named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). AFF1 directly interacts with ARF19 and regulates its accumulation. Mutants defective in AFF1 display ARF19 protein hyperaccumulation, mild auxin resistance, and developmental defects. Together, our data suggest a new mechanism, namely control of ARF protein stability, in regulating auxin responsiveness.
2022-06-09 | GSE172353 | GEO
Project description:Bacillus tropicus strain:AOA-CPS1 Genome sequencing and assembly
| PRJNA591551 | ENA
Project description:Long noncoding RNAs (lncRNAs), non-protein-coding transcripts exceeding 200 nu-cleotides, are critical regulators of gene expression through chromatin remodeling, transcriptional modulation, and post-transcriptional modifications. While ionizing radiation (IR) induces cellular damage through direct DNA breaks, reactive oxygen species (ROS)-mediated oxidative stress, and bystander effects, the functional in-volvement of lncRNAs in radiation response remains incompletely characterized. Here, through genome-wide CRISPR activation (CRISPRa) screening in non-small cell lung cancer (NSCLC) cells, we identified LOC401312 as a novel radiosensitizing lncRNA, the stable overexpression of which significantly enhanced IR sensitivity. Tran-scriptomic profiling revealed that LOC401312 transcriptionally upregulates car-bamoyl-phosphate synthase 1 (CPS1), a mitochondrial enzyme involved in pyrimidine biosynthesis. Notably, CPS1 overexpression recapitulated the radiosensitization phe-notype observed with LOC401312 activation. Mechanistic investigations revealed that CPS1 suppresses the phosphorylation of ATM kinase (Ser1981) and XRCC1 protein levels, which are key mediators of DNA damage checkpoint activation and base exci-sion repair, respectively. This study establishes the LOC401312-CPS1-ATM/XRCC1 axis as a previously unrecognized regulatory network governing radiation sensitivity, highlighting the potential of lncRNA-directed metabolic rewiring to impair DNA re-pair fidelity. Our findings not only expand the functional landscape of lncRNAs in DNA damage response but also provide a therapeutic rationale for targeting the LOC401312-CPS1 axis to improve radiotherapy efficacy in NSCLC.
2025-04-18 | GSE294906 | GEO
Project description:The P-TEFb-containing super elongation complex (SEC) plays the essential role in transcriptional elongation control. The AF4/FMR2 family members AFF1 and AFF4 are the central scaffold proteins of SEC, associated with different human diseases. However, their specific roles in transcriptional control remain unclear. Here, we report that AFF1 and AFF4 show distinct genomic distribution patterns around TSS. AFF1 binds upstream of TSS, while AFF4 is enriched downstream of TSS. Pol II occupancies are reduced genome-widely after depletion of AFF1, but not AFF4. Interestingly, in a subset of active genes with broad AFF4 binding signature, AFF4 disruption causes slow elongation and early termination, while AFF1 deletion mirrors the transcriptional defects observed in the fast Pol II mutant. Furthermore, AFF4 knockdown leads to increased AFF1 levels at chromatin, and vice versa. In summary, our data demonstrate that AFF1 and AFF4 function, to some extent, antagonistically to ensure proper Pol II transcription.
2023-07-02 | GSE207812 | GEO
Project description:The P-TEFb-containing super elongation complex (SEC) plays the essential role in transcriptional elongation control. The AF4/FMR2 family members AFF1 and AFF4 are the central scaffold proteins of SEC, associated with different human diseases. However, their specific roles in transcriptional control remain unclear. Here, we report that AFF1 and AFF4 show distinct genomic distribution patterns around TSS. AFF1 binds upstream of TSS, while AFF4 is enriched downstream of TSS. Pol II occupancies are reduced genome-widely after depletion of AFF1, but not AFF4. Interestingly, in a subset of active genes with broad AFF4 binding signature, AFF4 disruption causes slow elongation and early termination, while AFF1 deletion mirrors the transcriptional defects observed in the fast Pol II mutant. Furthermore, AFF4 knockdown leads to increased AFF1 levels at chromatin, and vice versa. In summary, our data demonstrate that AFF1 and AFF4 function, to some extent, antagonistically to ensure proper Pol II transcription.
2023-07-02 | GSE224754 | GEO
Project description:The P-TEFb-containing super elongation complex (SEC) plays the essential role in transcriptional elongation control. The AF4/FMR2 family members AFF1 and AFF4 are the central scaffold proteins of SEC, associated with different human diseases. However, their specific roles in transcriptional control remain unclear. Here, we report that AFF1 and AFF4 show distinct genomic distribution patterns around TSS. AFF1 binds upstream of TSS, while AFF4 is enriched downstream of TSS. Pol II occupancies are reduced genome-widely after depletion of AFF1, but not AFF4. Interestingly, in a subset of active genes with broad AFF4 binding signature, AFF4 disruption causes slow elongation and early termination, while AFF1 deletion mirrors the transcriptional defects observed in the fast Pol II mutant. Furthermore, AFF4 knockdown leads to increased AFF1 levels at chromatin, and vice versa. In summary, our data demonstrate that AFF1 and AFF4 function, to some extent, antagonistically to ensure proper Pol II transcription.
2023-07-02 | GSE224753 | GEO
Project description:The P-TEFb-containing super elongation complex (SEC) plays the essential role in transcriptional elongation control. The AF4/FMR2 family members AFF1 and AFF4 are the central scaffold proteins of SEC, associated with different human diseases. However, their specific roles in transcriptional control remain unclear. Here, we report that AFF1 and AFF4 show distinct genomic distribution patterns around TSS. AFF1 binds upstream of TSS, while AFF4 is enriched downstream of TSS. Pol II occupancies are reduced genome-widely after depletion of AFF1, but not AFF4. Interestingly, in a subset of active genes with broad AFF4 binding signature, AFF4 disruption causes slow elongation and early termination, while AFF1 deletion mirrors the transcriptional defects observed in the fast Pol II mutant. Furthermore, AFF4 knockdown leads to increased AFF1 levels at chromatin, and vice versa. In summary, our data demonstrate that AFF1 and AFF4 function, to some extent, antagonistically to ensure proper Pol II transcription.
2023-07-02 | GSE207810 | GEO