Journal: Current Issues in Molecular Biology

Article Title: Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

doi: 10.3390/cimb44060169

Figure Lengend Snippet: Expression of GOT2 in KIRC and normal patients. ( A ) Differential expression of GOT2 between KIRC samples from TCGA database (Red, n = 523 samples) and normal human kidney samples from GTEx database (Blue, n = 100 samples). (* p < 0.05, *** p < 0.001) ( B ) Significant downregulation of GOT2 protein level in the CPTAC KIRC cohort, analyzed by UALCAN. KIRC: n = 110; Normal samples: n = 84. Z-values represent standard deviations from the median across samples. ( C ) Representative images of immunohistochemical (IHC) staining of GOT2 protein in normal kidney tissue (Patient ID: 2067; Staining: medium; Intensity: moderate; Quantity: 75–25%; Location: cytoplasmic/membranous) and KIRC tissue (Patient ID: 2176; Staining: low; Intensity: weak; Quantity: >75%; Location: cytoplasmic/membranous) from the HPA database. Scale bars: left, 100 μm; right, 25 μm. Antibody used in both samples: HPA018139.

Article Snippet: In this study, we checked the expression of GOT2 in the protein expression module of the HPA database (Human Protein Atlas, https://www.proteinatlas.org/ , accessed on 1 December 2021) [ , , ], and we analyzed the immunohistochemical results of GOT2 in tumor tissue (ID: 2176) and normal tissue (ID: 2067).

Techniques: Expressing, Quantitative Proteomics, Immunohistochemical staining, Immunohistochemistry, Staining

Journal: eLife

Article Title: Transcriptional cartography integrates multiscale biology of the human cortex

doi: 10.7554/eLife.86933

Figure Lengend Snippet: ( a ) Overview of weighted gene co-expression network analysis (WGCNA) pipeline applied to the full dense expression map (DEM) dataset. Starting top left: the pairwise DEM spatial correlation matrix is used to generate a topological overlap matrix between genes (middle top), which is then clustered. Of the 23 WGCNA-defined modules, 7 were significantly enriched for non-cortical genes and removed, leaving 16 modules. Each module is defined by a set of spatially co-expressed genes, for which the principal component of expression can be computed and mapped at each cortical point (eigenmap). M6 is shown as an example projected onto an inflated left hemisphere (M6 z-scored expression and M6 expression change), and the bulk transcriptional distinctiveness (TD) terrain view from (M6 expression). ( b ) The extremes of WGCNA eigenmaps highlight different peaks in the cortical terrain: the main TD terrain colored by TD value (center, from ), surrounded by TD terrain projections of selected WGCNA eigenmaps. ( c ) WGCNA modules (eigenmaps and gradient maps, rows) are enriched for multiscale aspects of cortical organization (columns). Cell color intensity indicates pairwise statistical significance (p<0.05), while black outlines show significance after correction for multiple comparisons across modules. Columns capture key levels of cortical organization at different spatial scales (arranged from macro- to microscale) and developmental epochs: spatial alignment between module eigenmaps and in vivo MRI maps of cortical folding orientation, cortical thickness and T1/T2 ratio, fMRI resting-state functional networks; enrichment for module gene sets for independent annotations marking: cortical layers ( ; ); cell types ( ; ; ; ; ; ; ; ; ); subcellular compartments ; synapse-related genes ; protein–protein interactions between gene products ; temporal epochs of peak expression (‘fetal’: 8–24 21 post conception weeks [PCW]/’‘perinatal’' 24 PCW–6 mo/‘postnatal’ > 6 mo); transient layers of the mid-fetal human cortex at 21 PCW (subpial granular zone [SG], marginal zone [MZ], cortical plate [CP], subplate [SP], intermediate zone [IZ], subventricular zone [SZ], and ventricular zone [VZ]); and fetal cell types at 17–18 PCW . ( d ) Independent validation of multiscale enrichments for selected modules M2 and M12. M2 significantly overlaps the Neurosynth topic associated with the terms motor, cortex, and hand. Two high-ranking M2 genes, MOG and TF, exhibit clear layer VI peaks on in situ hybridization (ISH) and GO enrichment analysis myelin-related annotations. M12, overlapping the limbic network most closely overlapped the Neurosynth topic associated with social reasoning. Two high-ranking M22 genes GABRA2 and GRIN2B showed layer II ISH peaks and GO enrichment analysis revealed synaptic annotations. ( e ) Network visualization of pairwise overlaps between annotational gene sets used in (c), including WGCNA module gene sets (inset expression eigenmaps).

Article Snippet: Cellular compartment gene lists were taken from the COMPARTMENTS database , which identifies subcellular localisation of marker genes based on integrated information from the Human Protein Atlas, literature mining, and GO annotations.

Techniques: Expressing, In Vivo, Functional Assay, Protein-Protein interactions, Biomarker Discovery, In Situ Hybridization

Journal: Frontiers in Oncology

Article Title: Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

doi: 10.3389/fonc.2024.1371934

Figure Lengend Snippet: APOL1 is highly expressed in clear cell renal cell carcinoma. (A–C) Heat map of hierarchical clustering (A) , multidimensional scaling (B) and APOL1 mRNA expression (C) in RNA-seq of 9 patient ccRCC tumors compared to their adjacent normal tissues. (D) Kaplan-Meier survival analysis based on the APOL1 expression at stage 4 and grade 4 in the TCGA-KIRC dataset. (E, F) qRT-PCR analysis of APOL1 mRNA (E) and western blot analysis of APOL1 protein (F) in A-498, 786-O (primary cancer) and Caki-1 (metastatic) cells compared to HK-2 (normal) cells. Actin served as an internal control.

Article Snippet: In the Human Protein Atlas database, APOL1 notably has the highest RNA expression level in many kidney cancer cell lines compared to other cancer types ( ).

Techniques: Expressing, RNA Sequencing, Quantitative RT-PCR, Western Blot, Control

Journal: Frontiers in Oncology

Article Title: Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

doi: 10.3389/fonc.2024.1371934

Figure Lengend Snippet: miR-30a-3p suppresses APOL1 expression. (A–C) Heat map of hierarchical clustering (A) , multidimensional scaling (B) and miR-30a-3p expression (C) in miRNA-seq of 9 patient ccRCC tumors compared to their adjacent normal tissues. (D) Pearson correlation analysis between miR-30a-3p and APOL1 in patient ccRCC tumors. (E) Kaplan-Meier survival analysis based on the miR-30a expression in the TCGA-KIRC dataset. (F) Western blot analysis of APOL1 protein in control and miR-30a transfected A-498 and 786-O cells. Actin served as an internal control.

Article Snippet: In the Human Protein Atlas database, APOL1 notably has the highest RNA expression level in many kidney cancer cell lines compared to other cancer types ( ).

Techniques: Expressing, Western Blot, Control, Transfection

Journal: Frontiers in Oncology

Article Title: Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

doi: 10.3389/fonc.2024.1371934

Figure Lengend Snippet: APOL1 overexpression in renal cell carcinoma reduces the metastasis in vitro and in vivo . (A–C) Western blot analysis of APOL1 protein in control and APOL1 knockdown A-498 cells (A) , APOL1 knockdown 786-O cells (B) and APOL1 overexpressing Caki-1 cells (C) . Actin served as an internal control. (D, F, H) Wound healing analysis of control and APOL1 knockdown A-498 cells (D) , APOL1 knockdown 786-O cells (F) and APOL1 overexpressing Caki-1 cells (H) . Scale bar, 100 µM. (E, G, I) Transwell migration and invasion analysis of control and APOL1 knockdown A-498 cells (E) , APOL1 knockdown 786-O cells (G) and APOL1 overexpressing Caki-1 cells (I) cells. Scale bar, 100 µM. (J, K, L) Number of lung metastatic nodules (J) , representative image of the dissected lung (K) and H&E staining of lung (L) in mice intravenously injected with control and APOL1 overexpressing Caki-1 cells. Scale bar, 100 µM.

Article Snippet: In the Human Protein Atlas database, APOL1 notably has the highest RNA expression level in many kidney cancer cell lines compared to other cancer types ( ).

Techniques: Over Expression, In Vitro, In Vivo, Western Blot, Control, Knockdown, Migration, Staining, Injection

Journal: Frontiers in Oncology

Article Title: Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

doi: 10.3389/fonc.2024.1371934

Figure Lengend Snippet: APOL1 suppression activates Akt signaling pathway in clear cell renal cell carcinoma. (A) GSEA of RNA-seq data from patient ccRCC tumors compared to their adjacent normal tissues. (B) Gene enrichment analysis of 212 upregulated genes in patient ccRCC tumors. (C, D) Western blot analysis of Akt, NFĸB, GSK3β protein in control and APOL1 knockdown/overexpressing renal cells (C) , and miR-30a transfected A-498 and 786-O cells (D) . (E) Western blot analysis of focal adhesion proteins in control and APOL1 knockdown A-498 cells, APOL1 knockdown 786-O cells and APOL1 overexpressing Caki-1 cells. (F) Western blot analysis of EMT markers in control and APOL1 knockdown A-498 cells, APOL1 knockdown 786-O cells and APOL1 overexpressing Caki-1 cells. Actin served as an internal control.

Article Snippet: In the Human Protein Atlas database, APOL1 notably has the highest RNA expression level in many kidney cancer cell lines compared to other cancer types ( ).

Techniques: RNA Sequencing, Western Blot, Control, Knockdown, Transfection

Journal: Frontiers in Oncology

Article Title: Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

doi: 10.3389/fonc.2024.1371934

Figure Lengend Snippet: Schematics of APOL1 function in clear cell renal cell carcinoma. APOL1 attenuates renal cancer cell dissemination through FAK/Akt/GSK3β and NFκB-mediated EMT. miR-30a-3p inhibits APOL1 expression.

Article Snippet: In the Human Protein Atlas database, APOL1 notably has the highest RNA expression level in many kidney cancer cell lines compared to other cancer types ( ).

Techniques: Expressing