ARL4C remarkably promotes the tumorigenesis of Uveal Melanoma and may represent a potential therapeutic target

Uveal melanoma is the most common primary intraocular neoplasm, arising from melanocytes of the choroid plexus, ciliary body, and iris of the eye. The mechanism of tumorigenesis in uveal melanoma still remains unclear, resulting in poor outcomes of systemic therapies available for the treatment of uveal melanoma. Currently, ADP-ribosylation factor-like 4C (ARL4C), an ARF-Like small GTP-binding protein, has been confirmed to be closely involved in the occurrence of various tumors, including colorectal, lung, liver, gastric and ovarian cancers as well as glioblastoma. Here, we found that ARL4C was strongly expressed in uveal melanoma cells and widely distributed in the cytosol and nucleus. The proliferation and metastasis capabilities of OCM-1 and 92-1 uveal melanoma cells were significantly decreased after ARL4C knockdown both in vitro and in vivo. Furthermore, over-expression of ARL4C in ARL4C-depleted cells can significantly rescue the abilities of proliferation and metastasis in above both cells. In addition, direct injection of ARL4C small interfering RNA (siRNA) into OCM-1 cell-derived tumors inhibited tumor growth in immunodeficient mice. Therefore, ARL4C tightly participates in tumorigenesis and might represent a novel therapeutic target to uveal melanoma. We believe that small molecule drugs targeting ARL4C could be explored and further applied to clinical therapy of uveal melanoma in years or decades to come.