Long noncoding RNA CCAT2 is activated by E2F1 and exerts oncogenic properties by interacting with PTTG1 in pituitary adenomas

Am J Cancer Res. 2018 Feb 1;8(2):245-255. eCollection 2018.

Abstract

Pituitary adenomas, arising from the pituitary gland cells, are one of the most frequent tumors found in the sella region. However, the molecular mechanisms involved in the carcinogenesis and progression of pituitary adenomas is still not understood in detail. Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2), a newly identified lncRNA, has been reported to be abnormally expressed in some cancers. In the present study, we found that CCAT2 was significantly upregulated in pituitary adenomas tissues. Elevated CCAT2 expression was correlated with poor prognosis in patients with pituitary adenomas. Moreover, CCAT2 expression was activated by E2F1. Loss-of-function and gain-of-function assays showed that CCAT2 positively regulated pituitary adenoma cell proliferation, migration, and invasion. Further investigation demonstrated that CCAT2 interacted with PTTG1, and promoted its stability. Furthermore, CCAT2 affected the expression of downstream genes regulated by PTTG1, including SOX2, DLK1, MMP2, and MMP13. Cumulatively, CCAT2 functions as an oncogene in pituitary adenomas and its overexpression contributes to pituitary adenoma carcinogenesis and progression.

Keywords: CCAT2; PTTG1; pituitary adenomas.