Kim Kyungwon, Shin Hye Ju, Park Sang-Cheol, Kim Youngsook, Lee Min-Ho, Moon Ju Hyung, Kim Eui Hyun, Lee Eun Jig, Kang Chan Woo, Ku Cheol Ryong
Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
Artificial Intelligence and Robotics Laboratory, Myongji Hospital, Goyang, Republic of Korea.
J Endocrinol Invest. 2025 Feb;48(2):333-344. doi: 10.1007/s40618-024-02447-7. Epub 2024 Oct 3.
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 48 h in GH3 cells (P = 0.026). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72 h, P<0.001) and invasion (96.87% at 48 h, 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.
我们旨在鉴定生长激素（GH）分泌型垂体瘤中差异表达的剪接体成分，并研究它们在发病机制中的作用。
我们对20例生长激素腺瘤和6例正常垂体组织进行了转录组分析，以筛选失调的剪接体成分。基于64例肢端肥大症患者的基因表达分析临床特征。研究了GH分泌型垂体腺瘤细胞的增殖、侵袭和激素活性。
TCERG1在生长激素腺瘤中的表达明显高于正常垂体（log2倍数变化0.59，校正P = 0.0002）。基因型-表型分析显示，TCERG1表达较高的患者手术缓解率低于表达较低的患者（63.64%对95.45%，P = 0.009）。在海绵窦（CS）侵袭或Ki67指数超过3的组中，TCERG1表达明显更高（所有P>0.05）。TCERG1过表达导致GH3细胞增殖增加29.60%（P<0.001），48小时后侵袭增加249.4７%（P = 0.026）。相反，TCERG1沉默显著降低细胞增殖（72小时时降低25.76%，P<0.001）和侵袭（48小时时降低96.87%，P = 0.029）。在TCERG1过表达的GH3细胞和生长激素腺瘤中E-钙黏蛋白减少，但波形蛋白增加。并且TCERG1沉默逆转了GH3细胞中基因（CDH2、SNAI1、ZEB2和VIM）的表达。
剪接体机制为GH分泌型垂体瘤的发病机制提供了新的见解，并突出了TCERG1作为肿瘤侵袭性生物标志物的潜在作用。
