Supplementary Figures S1 through S11. (1) Supplementary Figure S1 shows the ectopical overexpressing of SATB2-AS1 in two CRC cell lines by lentivirus delivery. (2) Supplementary Figure S2 shows the effect of SATB2-AS1 on apoptosis in CRC cells. (3) Supplementary Figure S3 shows the effect of SATB2-AS1 knockdown mediated by siRNA on CRC cell proliferation, invasion and migration in vitro. (4) Supplementary Figure S4 shows the expression levels of SATB2 mRNA in CRC and adjacent non-cancerous tissues. (5) Supplementary Figure S5 shows the regulatory effect of SATB2-AS1 expression by SATB2. (6) Supplementary Figure S6 shows the effect of SATB2-AS1 on SATB2 mRNA stability. (7) Supplementary Figure S7 shows the enrichment amount of ZEB1-AS1 and PACER RNA with the p300 antibody by RIP assay. (8) Supplementary Figure S8 shows the regulatory effect of SATB2-AS1 on p300 mRNA. (9) Supplementary Figure S9 shows the inhibitory effects of SATB2-AS1 on M5 cells requiring p300 and SATB2. (10) Supplement Figure S10 shows the occupancy ability of p300 on Snail promoter by ChIP assay. (11) Supplementary Figure S11 shows the regulatory effect of Snail on SATB2-AS1 expression.
Funding
National Basic Research Program of China
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
ARTICLE 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 (SATB2-AS1), as a key regulator of colorectal carcinoma progression. SATB2-AS1 was frequently downregulated in colorectal carcinoma 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 colorectal carcinoma. SATB2-AS1 suppressed colorectal carcinoma 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 colorectal carcinoma 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 colorectal carcinoma.
These data show that the lncRNA SATB2-AS1 mediates epigenetic regulation of SATB2 and Snail expression to suppress colorectal cancer progression.See related commentary by Li, p. 3536