STING promotes invasion and migration of uveal melanoma through p38‑MAPK signaling

Oncol Rep. 2024 Feb;51(2):23. doi: 10.3892/or.2023.8682. Epub 2023 Dec 15.

Abstract

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, with a lack of effective treatment for metastasis and a poor prognosis. Stimulator of interferon genes (STING, also known as TMEM173) plays an important role in tumor development by regulating cell proliferation, metastasis and other cellular processes. However, the function of STING in UM remains unclear and requires further investigation. The present study analyzed the expression status of STING to elucidate the mechanisms underlying UM. The correlation between STING and the prognosis of UM was evaluated based on UM RNA‑seq data and clinical information extracted from The Cancer Genome Atlas database. Quantification of STING in UM cell lines and tissues was performed using the Wes Separation protein immunoassay. The effects of STING on the proliferation, migration and invasion of UM cells were investigated using Cell Counting Kit‑8, Transwell and wound healing experiments. Survival analysis demonstrated that high levels of STING in UM tissues indicated a poor prognosis. The expression of STING in UM tissues was higher than that in the choroid membranes. Furthermore, it was found that downregulation of STING expression in UM cells suppressed migration and invasion, whereas overexpression of STING significantly promoted migration and invasion. Notably, STING had no significant effect on UM cell proliferation. It was also identified that STING positively upregulated the phosphorylation of p38 mitogen‑activated protein kinase (p38‑MAPK) in UM cells, enhancing cell migration and invasion, which the p38‑MAPK inhibitor SB203580 reversed. Finally, the results of the present study demonstrated that high STING expression in UM indicates a poor prognosis. STING was revealed to promote the migration and invasion of UM cells through p38‑MAPK signaling.

Keywords: STING; invasion; migration; p38‑MAPK; uveal melanoma.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • MAP Kinase Signaling System / genetics
  • Melanoma* / pathology
  • Uveal Neoplasms* / genetics
  • Uveal Neoplasms* / metabolism
  • Uveal Neoplasms* / pathology

Supplementary concepts

  • Uveal melanoma