Journal
ONCOTARGET
Volume 7, Issue 8, Pages 9175-9187Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7037
Keywords
Cushing's disease; cold inducible RNA binding protein; Erk pathway
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Funding
- National Natural Science Foundation of China [81270856]
- National High technology Research and Development Program (863 program) of China [2014AA020611]
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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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