Fig. 3: SEs control the expression of cancer stemness genes and pro-metastatic genes. | Nature Communications

Fig. 3: SEs control the expression of cancer stemness genes and pro-metastatic genes.

From: Transcriptional super-enhancers control cancer stemness and metastasis genes in squamous cell carcinoma

Fig. 3

a Knockdown of TP63 inhibited tumorsphere formation by ALDHhighCD44high CSC-like cells from SCC1 cells. Values are mean ± SD for triplicate experiments. Statistical analysis was performed using two-tailed unpaired Student’s t-test. Scale bar, 200 μm. b Knockdown of TP63 inhibited tumorsphere formation by CSCs from the HNSCC PDXs. Values are mean ± SD for triplicate experiments. Statistical analysis was performed using two-tailed unpaired Student’s t-test. Scale bar, 200 μm. c The signals for MED1, BRD4, and p65 were highly enriched at the SE region of TP63. d ChIP-qPCR showed that JQ1 treatment significantly reduced the occupancy of p65, BRD4, and MED1 on the SE region of TP63 (n = 3 per group). e The signals for MED1, BRD4, and p65 were highly enriched at the SE region of MET. f ChIP-qPCR showed that JQ1 treatment significantly reduced the occupancy of p65, BRD4, and MED1 on the SE region of MET (n = 3 per group). g The signals for MED1, BRD4, and p65 were highly enriched at the SE region of BIRC3. h ChIP-qPCR showed that JQ1 treatment significantly reduced the occupancy of p65, BRD4, and MED1 on the SE region of BIRC3 (n = 3 per group). i The signals for MED1, BRD4, and p65 were highly enriched at the SE region of MMP3. j ChIP-qPCR showed that JQ1 treatment significantly reduced the occupancy of p65, BRD4, and MED1 on the SE region of MMP3 (n = 3 per group). k Schematic showing targeting SEs using a catalytically dead Cas9 (dCas9) associated with either a transcriptional activator (SAM) or repressor complex (KRAB-MeCP2). l RT-qPCR showed that MMP3 and TP63 expression was significantly enhanced or inhibited in SCC1 cell following introducing the dCas9-SAM or dCas9-KRAB system targeting SE regions (n = 3 per group). m TP63-SE and TP63-NEG activities were measured by luciferase reporter assays (n = 4 per group). Data are presented as mean values ± SD in d, f, h, j, l, and m. Statistical analysis was performed using two-tailed unpaired Student’s t-test. The data are representative of three experiments with similar results. Source data are provided as a Source data file.

Back to article page