STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma

• Published in: Cell death & disease Vol. 15; no. 10; pp. 713 - 13
• Main Authors: Liu, Bo, Yao, Xueting, Huang, Qinying, Fan, Yichao, Yu, Bo, Wang, Jing, Wu, Wencan, Dai, Jinhui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2024; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/80/39; 692/699/67/1484; Animals; Antibodies; Apoptosis; Autophagy; Autophagy - drug effects; Biochemistry; Bioinformatics; Biomarkers; Biomedical and Life Sciences; Cancer; Cell Biology; Cell Culture; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cytokines; Disease; Female; Gene expression; Gene Expression Regulation, Neoplastic; Hospitals; Humans; Immune system; Immunology; Life Sciences; Male; Medical prognosis; Medical research; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, Inbred BALB C; Mice, Nude; mRNA; Mutation; Ophthalmology; Patients; Proteins; Signal Transduction; Stat6 protein; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - metabolism; Therapeutic targets; Tumorigenesis; Tumorigenicity; Uveal Neoplasms - drug therapy; Uveal Neoplasms - genetics; Uveal Neoplasms - metabolism; Uveal Neoplasms - pathology; Zoledronic acid; Zoledronic Acid - pharmacology
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-024-07115-5

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.