Abstract
The tumor microenvironment (TME) and activated angiogenesis in thyroid carcinoma (TC) are critical for tumor growth and metastasis. Nuclear receptor binding protein 2 (NRBP2) has been suggested as a tumor suppressor. This study examines the function of NRBP2 in the progression of TC and the regulatory mechanism. By analyzing bioinformatic tools including GSE165724 dataset and the Cancer Genome Atlas system, we predicted NRBP2 as a poorly expressed gene in TC. Decreased NRBP2 expression was detected in TC tumor tissues and cells. Poor expression of NRBP2 was linked to unfavorable prognosis of patients. GATA binding protein 1 (GATA1) was found as a negative regulator of NRBP2. It recruited histone deacetylase2 (HDAC2) to the NRBP2 promoter to trigger histone deacetylation. NRBP2 overexpression suppressed growth of TC cells, and it reduced expression of TME markers, M2 polarization of macrophages, and angiogenesis in TC. Similar results were reproduced in vivo in nude mice. However, the anti-oncogenic roles of NRBP2 were blocked after further overexpression of GATA1 or HDAC2. In summary, this study demonstrates that GATA1 recruits HDAC2 to the NRBP2 promoter and enhances the TME and angiogenesis in TC cells.