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STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma.
- Source :
-
Cell death & disease [Cell Death Dis] 2024 Oct 01; Vol. 15 (10), pp. 713. Date of Electronic Publication: 2024 Oct 01. - Publication Year :
- 2024
-
Abstract
- Compelling evidence has revealed a novel function of the STAT pathway in the pathophysiology of uveal melanoma (UM); however, its regulatory mechanisms remain unclear. Here, we analyzed the clinical prognostic value of STAT family genes in UM patients using bioinformatics approaches and found that high STAT6 expression is associated with poor prognosis. Furthermore, cellular experiments and a nude mouse model demonstrated that STAT6 promotes UM progression through the autophagy pathway both in vivo and in vitro. Next, RIP-PCR revealed that STAT6 protein binds to LINC01637 mRNA, which in turn regulates STAT6 expression to promote UM growth. Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Animals
Cell Line, Tumor
Mice
Gene Expression Regulation, Neoplastic
Zoledronic Acid pharmacology
Male
Female
Mice, Inbred BALB C
Signal Transduction
Autophagy drug effects
Uveal Neoplasms pathology
Uveal Neoplasms metabolism
Uveal Neoplasms genetics
Uveal Neoplasms drug therapy
Melanoma pathology
Melanoma metabolism
Melanoma genetics
Melanoma drug therapy
Mice, Nude
STAT6 Transcription Factor metabolism
STAT6 Transcription Factor genetics
Cell Proliferation
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 15
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 39353898
- Full Text :
- https://doi.org/10.1038/s41419-024-07115-5