Figure 6.
SOX11 shares similar transcriptional roles in MCL and BL. (A) Dot plot showing at the x-axis the normalized enrichment score (NES), and at the y-axis the SOX11-target genes identified in our previously studies in MCL cell lines by chromatin immunoprecipitation (ChIP) with DNA microarray (chip; SOX11-direct targets in MCL), upregulated (SOX11 MCL signature-UP), or downregulated (SOX11 MCL signature-Down) in SOX11+ compared with SOX11− MCL cell line (Z138CT vs Z138SOX11KO) and primary samples (conventional molecular subtype [cMCL] vs nonnodal MCL subtype [nnMCL]), enriched in SOX11+ compared with SOX11− BL cell lines (DG75 ER RE-SOX11 vs DG75 ER; Ramos-SOX11+ vs Ramos CT; BL2CT vs BL2-SOX11KO). Outlined in color codes is the false discovery rate. Size of bubbles represent number of enriched genes. (B) Overlap between DEG in 4-OHT–treated DG75 ER-SOX11 BL cell line (in yellow, 1660 genes with gene symbol), upon SOX11 KO in Z138 MCL cell line (in green, 686 genes with gene symbol), and SOX11-direct target genes in MCL found by ChIP on chip in Z138 cell line (in blue, 1909 genes with gene symbol). (C) Pathway enrichment analysis on common genes between DEG in DG75 ER-SOX11 BL cells, and upon SOX11 KO in Z138 MCL cells and SOX11 targets genes obtained by ChIP on chip in Z138 MCL cells (red circle). Number of genes, fold enrichment, and –log10(P value) for each pathway are shown. (D) PLXNB1, CD24, and MEX3A relative mRNA expression (normalized to glucuronidase beta [GUSB] gene endogenous control) in BL and MCL SOX11-overexpressing cell lines (left, Ramos-SOX11+, DG75 ER-SOX11, and JVM2-SOX11+), and in SOX11-KO BL and MCL cell lines (right, BL2-SOX11KO and Z138-SOX11KO). Data are shown as mean ± standard deviation of the fold change between SOX11-overexpressing or SOX11-KO and its respective control cell values, obtained in 3 independent experiments. Statistical significance was obtained by unpaired 2-tailed t test. (E) Western blot experiments showing MEX3A and SOX11 protein levels (ER-SOX11, SOX11-FLAG, or endogenous SOX11) in BL2-CT, DG75 ER-SOX11, and Ramos-SOX11+ and their control cell lines BL2-SOX11KO CT, DG75 ER, and Ramos CT. Tubulin was used as a loading control. (F) Histograms showing CD24 protein levels analyzed by flow cytometry in SOX11− (Z138-SOX11KO and BL-SOX11KO) MCL and BL cell line models and their respective SOX1+ control cells. CD24 staining is shown in filled dark blue histograms for SOX11+ cells and in filled light-blue histograms for SOX11− cells, whereas isotype controls are shown in nonfilled and long-dashed histograms. (G) CXCR5, CCR7, and ITGB7 mRNA expression levels (log2-transformed values) in DG75 ER and DG75 ER-SOX11, obtained by RNA sequencing. (H) Relative adhesion to VCAM-1 measured as the ratio of fluorescence emission of calcein-labeled cells between those that have been attached to untreated microplate wells precoated with VCAM-1 and those attached in an unspecific way (VCAM-1 adhesion/unspecific cell adhesion in bovine serum albumin [BSA] 0.5%). Statistical significance was obtained by unpaired 2-tailed t test. ∗P < .05; ∗∗P < .01, ∗∗∗P < .001; ∗∗∗∗P < .0001.

SOX11 shares similar transcriptional roles in MCL and BL. (A) Dot plot showing at the x-axis the normalized enrichment score (NES), and at the y-axis the SOX11-target genes identified in our previously studies in MCL cell lines by chromatin immunoprecipitation (ChIP) with DNA microarray (chip; SOX11-direct targets in MCL), upregulated (SOX11 MCL signature-UP), or downregulated (SOX11 MCL signature-Down) in SOX11+ compared with SOX11 MCL cell line (Z138CT vs Z138SOX11KO) and primary samples (conventional molecular subtype [cMCL] vs nonnodal MCL subtype [nnMCL]), enriched in SOX11+ compared with SOX11 BL cell lines (DG75 ER RE-SOX11 vs DG75 ER; Ramos-SOX11+ vs Ramos CT; BL2CT vs BL2-SOX11KO). Outlined in color codes is the false discovery rate. Size of bubbles represent number of enriched genes. (B) Overlap between DEG in 4-OHT–treated DG75 ER-SOX11 BL cell line (in yellow, 1660 genes with gene symbol), upon SOX11 KO in Z138 MCL cell line (in green, 686 genes with gene symbol), and SOX11-direct target genes in MCL found by ChIP on chip in Z138 cell line (in blue, 1909 genes with gene symbol). (C) Pathway enrichment analysis on common genes between DEG in DG75 ER-SOX11 BL cells, and upon SOX11 KO in Z138 MCL cells and SOX11 targets genes obtained by ChIP on chip in Z138 MCL cells (red circle). Number of genes, fold enrichment, and –log10(P value) for each pathway are shown. (D) PLXNB1, CD24, and MEX3A relative mRNA expression (normalized to glucuronidase beta [GUSB] gene endogenous control) in BL and MCL SOX11-overexpressing cell lines (left, Ramos-SOX11+, DG75 ER-SOX11, and JVM2-SOX11+), and in SOX11-KO BL and MCL cell lines (right, BL2-SOX11KO and Z138-SOX11KO). Data are shown as mean ± standard deviation of the fold change between SOX11-overexpressing or SOX11-KO and its respective control cell values, obtained in 3 independent experiments. Statistical significance was obtained by unpaired 2-tailed t test. (E) Western blot experiments showing MEX3A and SOX11 protein levels (ER-SOX11, SOX11-FLAG, or endogenous SOX11) in BL2-CT, DG75 ER-SOX11, and Ramos-SOX11+ and their control cell lines BL2-SOX11KO CT, DG75 ER, and Ramos CT. Tubulin was used as a loading control. (F) Histograms showing CD24 protein levels analyzed by flow cytometry in SOX11 (Z138-SOX11KO and BL-SOX11KO) MCL and BL cell line models and their respective SOX1+ control cells. CD24 staining is shown in filled dark blue histograms for SOX11+ cells and in filled light-blue histograms for SOX11 cells, whereas isotype controls are shown in nonfilled and long-dashed histograms. (G) CXCR5, CCR7, and ITGB7 mRNA expression levels (log2-transformed values) in DG75 ER and DG75 ER-SOX11, obtained by RNA sequencing. (H) Relative adhesion to VCAM-1 measured as the ratio of fluorescence emission of calcein-labeled cells between those that have been attached to untreated microplate wells precoated with VCAM-1 and those attached in an unspecific way (VCAM-1 adhesion/unspecific cell adhesion in bovine serum albumin [BSA] 0.5%). Statistical significance was obtained by unpaired 2-tailed t test. ∗P < .05; ∗∗P < .01, ∗∗∗P < .001; ∗∗∗∗P < .0001.

or Create an Account

Close Modal
Close Modal