Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.

Abstract

We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis. We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated. TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001*) and a 249.47% increase in invasion after 48h in GH3 cells (P = 0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72h, P<0.001*) and invasion (96.87% at 48h, P = 0.029*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.