Skip to main content
. 2021 Jul 8;10:e64212. doi: 10.7554/eLife.64212

Figure 8. MGA has tumor suppressive functions in colorectal cancer.

(A) GENIE and TCGA consortium data depicting alterations at the MGA locus in colorectal cancer. (B) Western blot for MGA, L3MBTL2, and MAX in Empty and sgMGA normal colon organoids. (C) Representative images and (D) quantification of normal human colon organoid growth from single cells following MGA inactivation using CRISPR (*p=8.84e−10. Two-sided Student’s t-test, n = 18 FOV across six biological replicates). (E) PCA plots for Empty and sgMGA organoids (n = 4 biological replicates for each). (F) Normalized CPM values for MGA target genes in Empty and sgMGA organoids (n = 4 biological replicates for each). GSEA Hallmark and Reactome analysis for genes (G) upregulated and (H) downregulated upon MGA loss in colon organoids (FDR < 0.05, LFC > 1.5). (I) Proposed mechanism of MGA mediated tumor suppressive effects: MGA acts as a scaffold and stabilizes atypical PRC1.6 members, including L3MBTL2. Under normal conditions, this results in the repression or transcriptional attenuation of thousands of genes. During malignant progression, perturbation of MGA expression leads to the upregulation of growth-promoting and pro-invasive PRC1.6, MYC, and E2F targets in a tissue-specific manner.

Figure 8—source data 1. MGA has tumor suppressive functions in colorectal cancer.
Source data related to Figure 8D,F,G, and H.

Figure 8.

Figure 8—figure supplement 1. MGA has tumor suppressive functions in colon cancer.

Figure 8—figure supplement 1.

(A) Immunofluorescent staining for MGA in 2D organoid cultures. (B) Sequencing to show indel formation in clonal sgMGA (#1 and #2) organoids compared to Empty vector transduced controls. (C) Growth of sgMGA and Empty organoids in 2D culture. (D) Timewise comparison of organoid growth of Empty and sgMGA transduced cells after single-cell seeding. (E) Heatmap showing colon cancer stem cell signature genes and senescence associated genes that are differentially expressed between Empty and sgMGA colon organoids (LFC > 1.5, FDR < 0.05).