Effects of suppressor of cytokine signaling 1 silencing on human melanoma cell proliferation and interferon-γ sensitivity

Abstract

The aim of the current study was to observe the effects of suppressor of cytokine signaling 1 (SOCS1) silencing in human melanoma cells on cell biological behavior and interferon-γ (IFN-γ) sensitivity, and to investigate the use of SOCS1 as a therapeutic target in the treatment of melanoma. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to verify that SOCS1 interference effectively silenced the expression of SOCS1 in the Mel526 human melanoma cell line. For IFN-γ stimulation, western blot analysis was used to observe changes in expression levels of signal transduction and transcription activator (STAT) 1 and phosphorylated STAT (pSTAT) 1. Changes in the expression levels of IFN-γ regulatory factor 1 (IRF-1) were measured with RT-qPCR. Changes in the sensitivity of melanoma cells to IFN-γ were detected using an MTT assay. The cell proliferation rate was observed by cell counting and changes in the cell cycle were detected with flow cytometry. The results revealed that SOCS1 interference effectively silences SOCS1 expression in Mel526 cells. However, the S stage of the cell cycle was markedly extended. Following the inhibition of SOCS1 expression, the proliferation experiment demonstrated that the proliferation ability of Mel526 cells was decreased. Following IFN-γ stimulation, the expression levels of pSTAT and IRF-1 increased significantly compared with those in the controls. The MTT experiment showed that SOCS1 interference caused the median inhibitory concentration (IC50) of oxaliplatin in Mel526 cells to decrease significantly. In conclusion, SOCS1 interference reduced the proliferation ability of Mel526 human melanoma cells and increased their sensitivity to IFN-γ.

Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis

“…In this way, SOCS modulates the ubiquitination of a variety of proteins, which are subsequently recognised by the proteasome and degraded. Parrillas et al (2013) previously reported that SOCS1 is associated with degradation of Cdh1 and blockades melanoma cells in mitosis by G2/M arrest via regulation of cyclin D and cyclin E. G1/S arrest was also reported in melanoma cells treated with a JAK inhibitor and was associated with reduced STAT3 activation ( Xu et al , 2015 ). In the present study, we found that SOCS1 had cell cycle inhibitory activity at the G2/M phase in GC cells.…”

Clinical correlation of liver function tests with suppression of cytokine signaling (SOCS1) gene expression in HCV infected patients: A real‐world clinical experience

“…The study further verified an inverse correlation between miR-221/222 expression and SOCS1 expression serum or in liver tissue in rats. 10 The results of Xu et al 11 The finding herein exhibited that ALT, AST, and ALP were positively correlated with SOCS1 gene expression but the exact mechanism behind this correlation needs further research.…”

“…The results of Xu et al proved SOCS1 as a vital target to influence therapeutic effects of melanoma because silencing SOCS1 expression in Mel526 cells reportedly influenced cell cycle, increased cell sensitivity to IFN‐γ, and inhibited the proliferation of tumor cells.…”

Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses

“…Deregulation of FOXO1 promotes cell proliferation and tumorigenesis, and has thus become a primary target of tumorigenesis prevention (48,49). IRF1 is involved in the regulation of interferon α and β transcription, and it has been demonstrated that IRF1 gene deletion or rearrangement correlates with the development of human cancers (50,51). The glucocorticoid receptor is a member of the nuclear receptor family, which acts as a ligand-dependent transcription factor to regulate gene expression.…”