Introduction: Gliomas are the most seen tumours in adults in the central nervous system, and high grade of gliomas cause the worse prognose of patients with a shorter survival period. Ubiquitin-specific protease 38 (USP38) has been regarded as the negative regulator of type I interferon signalling; it regulates the ubiquitination process of TANK binding kinase 1 (TBK1). Further study revealed that USP38 also stabilizes the protein lysine-specific histone demethylase 1A (LSD1) via cleaving the ubiquitin chain. However, the effect of USP38 in colorectal cancer was not fully understood.
Material and methods: USP38 overexpression and knockdown vector were constructed using the molecular clone method. The viability rate of U-87MG and U-138MG cells were detected using the Cell Counting Kit-8 (CCK-8) method.The expression and secretion of metastasis-related molecules were detected using the qPCR and ELISA method. The expression of metastasis-related molecules and JAK2/STAT3 signalling pathway was detected using western blotting analysis.
Results: In this study, we firstly constructed a USP38 overexpression and inhibition model in 2 cell lines and found that overexpression of USP38 inhibits the viability rate and migration ability of glioma cells. We further noticed that elevated expression of USP38 reduced the expression and secretion of cell adhesion-related molecules with the elevation in expression of pro-apoptotic proteins, and these effects might be mediated by inhibition of JAK2/STAT3 signalling pathway as USP38 is the upstream regulator of STAT3 and inhibition of cellular adhesion process.
Conclusions: USP38 might be a new therapeutic target for glioma.
Keywords: JAK2/STAT3 signalling pathway; LAMPs; MMPs; USP38; vemurafenib; glioma.