SATB2-AS1 suppresses colorectal carcinoma aggressiveness by inhibiting SATB2-dependent Snail transcription and epithelial-mesenchymal transition

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