<i>SATB2-AS1</i> Suppresses Colorectal Carcinoma Aggressiveness by Inhibiting SATB2-Dependent <i>Snail</i> Transcription and Epithelial–Mesenchymal Transition

Abstract

Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (<i>SATB2-AS1</i>), as a key regulator of colorectal carcinoma progression. <i>SATB2-AS1</i> was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed <i>SATB2-AS1</i> at low levels had a shorter overall survival and poorer prognosis. Downregulation of <i>SATB2-AS1</i> significantly promoted cell proliferation, migration, and invasion <i>in vitro</i> and <i>in vivo</i>, demonstrating that it acts as a tumor suppressor in colorectal carcinoma. <i>SATB2-AS1</i> suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the <i>SATB2</i> promoter upregulated expression of <i>SATB2</i>, a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the <i>Snail</i> promoter, repressing <i>Snail</i> transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal <i>SATB2-AS1</i> as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma. SIGNIFICANCE: These data show that the lncRNA <i>SATB2-AS1</i> mediates epigenetic regulation of <i>SATB2</i> and <i>Snail</i> expression to suppress colorectal cancer progression.<i>See related commentary by Li, p. 3536</i>.