BACKGROUND/AIM: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a mean incidence of 5.1 cases per million people per year. At least 40% of uveal melanoma patients ultimately develop distant metastasis. But unlike cutaneous melanoma, targeted therapies and immune checkpoint blockers have shown limited effects. Investigating the metastasis-related pathogenesis mechanisms of uveal melanoma could facilitate the development of potential therapies.

MATERIALS AND METHODS

For this purpose, we integrated microarray gene expression data (GSE22138) and an independent TCGA dataset to identify derlin-1 (DERL1) as our candidate gene. cellular assays were conducted to examine DERL1's role in the pathogenesis of uveal melanoma.

RESULTS

DERL1 up-regulation was identified in metastatic UM based on the microarray dataset, which was consistent with the TCGA dataset. However, the detailed mechanism has not yet been investigated. Therefore, we manipulated DERL1 expression with siRNA in a uveal melanoma cell line. After confirming the successful knockdown of DERL1, oncogenicity and chemosensitivity were assessed. Knockdown of DERL1 repressed cell proliferation and impaired cell migration and invasion. Furthermore, uveal melanoma cells with DERL1 knockdown had increased chemosensitivity to cisplatin and a decreased cancer stem cell potential determined by examining the intensity of CD133 and CD271.

CONCLUSION

By analyzing GEO and TCGA datasets combined with cellular assays, DERL1 was found to be associated with metastasis in uveal melanoma and to be a possible target for further treatment.