Enhanced expression of son of sevenless homolog 1 is predictive of poor prognosis in uveal malignant melanoma patients

Abstract

ABSTRACTPurpose: The work outlined herein investigated the prognosis value and the potential role son of sevenless homolog 1 (SOS1) played in uveal melanoma (UM).Methods: We analyzed the mRNA expression level of SOS1 in primary UM cells based on the GSE44295 dataset obtained from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) database. The correlation between SOS1 expression and clinical characteristics were analyzed by Chi-squared (χ2) test. Then we used SOS1 siRNA to downregulate SOS1 expression in M23 cells. The effect of knockdown SOS1 on cell proliferation was studied using the Cell-Counting Kit-8 and colony formation assays. The influence of silencing SOS1 on cell motility was explored using wound-healing assays and transwell assays. In addition, the relationship between SOS1 and the MAPK signaling pathway was analyzed by western blot.Results: Our results demonstrated that the mRNA expression level of SOS1 was markedly upregulated in UM cells (p < 0.001) and correlated with poor prognosis in UM patients (p = 0.015). Moreover, SOS1 mRNA expression level was found to be positively associated with histological-type (p = 0.043) and death (p = 0.012). Knockdown of SOS1 caused an inhibition on M23 cell proliferation, migration, and invasion. Moreover, the phosphorylation levels of MEK and ERK were reduced in UM cells after downregulating SOS1 expression (p < 0.010).Conclusion: Our data demonstrated that SOS1 might play a facilitating role in M23 cell growth and motility by regulating the MAPK signaling pathway. Furthermore, the data suggested that SOS1 may serve as an UM predictor of prognosis as well as a therapeutic target.