Arntl-induced upregulation of DUSP1 inhibits tumor progression in esophageal squamous cell carcinoma by inactivating ERK signaling
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View abstract on PubMed
Summary
This summary is machine-generated.Aryl hydrocarbon receptor nuclear translocator-like (ARNTL) suppresses esophageal squamous cell carcinoma (ESCC) growth by upregulating Dual-specificity protein phosphatase-1 (DUSP1), inhibiting ERK signaling and promoting apoptosis.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Esophageal squamous cell carcinoma (ESCC) presents high morbidity.
- The circadian clock gene Aryl hydrocarbon receptor nuclear translocator-like (ARNTL) is implicated in various cancers, but its role in ESCC is unclear.
Purpose Of The Study
- To investigate the function and molecular mechanisms of ARNTL in ESCC.
- To determine the relationship between ARNTL, Dual-specificity protein phosphatase-1 (DUSP1), and ERK signaling in ESCC progression.
Main Methods
- Analyzed ARNTL expression using TCGA and qRT-PCR.
- Assessed cell viability, proliferation, and apoptosis in vitro and tumor growth in vivo.
- Investigated ARNTL downstream targets and DUSP1 regulation via luciferase reporter, ChIP, and RNA pull-down assays.
- Examined ERK signaling pathway activation using western blotting.
Main Results
- ARNTL expression was decreased in ESCC and associated with histological types.
- ARNTL upregulation inhibited ESCC cell viability and proliferation, induced apoptosis, and reduced tumor growth.
- ARNTL positively regulated DUSP1 transcription, and DUSP1 silencing reversed ARNTL's effects.
- ARNTL attenuated ERK signaling activation by decreasing ERK phosphorylation via DUSP1 upregulation.
Conclusions
- ARNTL acts as a tumor suppressor in ESCC.
- ARNTL inhibits ESCC cell growth and promotes apoptosis by inactivating ERK signaling through DUSP1 transcriptional upregulation.
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