Fig 1: Downregulated SLC25A38 boosts angiogenesis.A A proposed model underlying the role of SLC25A38 in UM angiogenesis. Through the promotion of the coactivator (CBP/p300) of HIF upon SLC25A38 knock-out, its target genes including pro-angiogenic factors are overexpressed and thus promote angiogenesis. GSEA of TCGA cohort and PCR validation of UM cells verified this proposal. B Correlation between SLC25A38 and CBP or CD31 protein expression in UM specimens. Tumor sections from 28 UM specimens were immunofluorescence stained with anti-SLC25A38, anti-CBP, and anti-CD31 antibodies. Left: representative images. Right: the correlation between SLC25A38 and CBP or CD31 protein expression was calculated by Pearson correlation coefficient. C Correlation between SLC25A38, CBP, FGF8, FGF12, TGFa, and CD31 expression in TCGA UM RNA-seq dataset. The Pearson correlation coefficient and P-value are indicated.
Fig 2: Model accuracy and survival analyses in UM.A–F Receiver Operator Curves based on different feature sets in TCGA cohort (A–C) and GSE22138 cohort (D–F). The predictive accuracy of SLC25A38 expression for risk of metastasis was superior to that of other biomarkers. The P-value in light blue in B indicates Binary SLC25A38 vs BAP1 Mut, and the P-value in dark blue in B indicates Binary SLC25A38 vs SF3B1 Mut. The P-value in light blue in C indicates Binary SLC25A38 vs Binary BAP1, and the P-value in dark blue in C indicates Binary SLC25A38 vs GEP Class. G–I Survival curves based on SLC25A38 expression level. Low expression of SLC25A38 predicted poor clinical outcomes not only in all patients but also in patients without metastasis or patients with disomy 3 in TCGA UM cohort. AUC Area Under Curve.
Fig 3: Silencing SLC25A38 promotes the malignant properties of UM cells in vitro and in vivo.A UM cells with SLC25A38 knock-out were successfully constructed. B, C Wound healing assay (B) and transwell invasion assay (C) showing that SLC25A38 knock-out could enhance the migration and invasion ability of UM cells. D Vascular ring formation analyses indicate the increasing ability of angiogenesis upon SLC25A38 knock-out. The number of tubes was counted and normalized tube length was calculated, scale bar 100 µm. E PET imaging and H&E staining showed that mice inoculated with SLC25A38 knock-out UM cells had more lung metastases and live metastases compared to that injected with control UM cells, scale bar 100 µm.
Fig 4: Gene expression profiling of primary uveal melanomas (UMs) based on metastatic status.A Volcano plots showing differentially expression genes between metastatic tumors and non-metastatic tumors in TCGA UM cohort. B Heatmap showing the 89 most highly downregulated genes located on chromosome 3. Blue: decreased gene expression, red: increased gene expression. C Molecular landscape in 80 primary UMs of TCGA cohort. Mutation or expression status for six genes, the metastatic status of tumor sample, and chromosome 3 copy number alterations are indicated. D SLC25A38 was highly expressed in tumors with disomy 3 in TCGA UM cohort.
Fig 5: SLC25A38 is the upstream of several metastasis-related pathways.A Pie chart illustrating differentially expression genes between SLC25A38-low tumors and SLC25A38-high tumors in TCGA UM RNA-seq dataset. B GSEA showing that SLC25A38 expression was negatively correlated with proliferative and metastatic gene signatures in the TCGA UM dataset. C Heatmap showing differentially expression genes in UM cells with SLC25A38 knock-out relative to control cells. D The most significant differentially GO items upon SLC25A38 knock-out. E Differentially expression genes in the SLC25A38-silenced UM cells in the indicated signaling pathways analyzed by qRT-PCR. F These series of networks demonstrated the changes in SLC25A38 and its neighboring genes (involving in cell proliferation, cell adhesion, cell motility, and angiogenesis) in terms of expression during metastasis in TCGA UM specimens and GSE22138 tumors.
Supplier Page from Abcam for Anti-SLC25A38 antibody [EPBHMR1]