GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma

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