Jian Fangfang, Chen Yufan, Ning Guang, Fu Wei, Tang Hao, Chen Xiao, Zhao Yao, Zheng Lili, Pan Sijian, Wang Weiqing, Bian Liuguan, Sun Qingfang
Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Oncotarget. 2016 Feb 23;7(8):9175-87. doi: 10.18632/oncotarget.7037.
Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence.
库欣病由垂体促肾上腺皮质激素腺瘤引起，其发病机制尚不清楚。在此，我们发现冷诱导RNA结合蛋白（CIRP）在促肾上腺皮质激素肿瘤中显著升高。在小鼠AtT20垂体促肾上腺皮质激素细胞系中强制过表达CIRP可增加促肾上腺皮质激素前体激素阿黑皮素原（POMC）转录、促肾上腺皮质激素（ACTH）分泌和细胞增殖。在体内，CIRP过表达促进小鼠促肾上腺皮质激素肿瘤生长并增强ACTH产生。机制上，我们表明CIRP可通过Erk1/2信号通路诱导细胞周期蛋白D1并降低p27表达来促进AtT20细胞增殖。临床上，CIRP过表达与库欣病复发显著相关。CIRP似乎在库欣病中发挥关键的肿瘤发生功能，其表达可能是肿瘤复发的有用生物标志物。
