Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway
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Fangfang Jian1,*, Yufan Chen1,*, Guang Ning4,*, Wei Fu1, Hao Tang1, Xiao Chen2, Yao Zhao3, Lili Zheng1, Sijian Pan1, Weiqing Wang4, Liuguan Bian1 and Qingfang Sun1,5
1 Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2 Department of Neurosurgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
3 Department of Neurosurgery, Shanghai Pituitary Tumor Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
4 Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
5 Department of Neurosurgery, Ruijin Hospital, Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China
* These authors have contributed equally to this work
Qingfang Sun, email:
Liuguan Bian, email:
Keywords: Cushing’s disease, cold inducible RNA binding protein, Erk pathway
Received: July 28, 2015 Accepted: January 19, 2016 Published: January 27, 2016
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.
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