Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: Identifying top transcription regulators by co-expression and motif analysis associated with the disease phenotypic status of neuroblastoma patients Unique transcription regulators differentiate neuroblastoma patients according to the risk (A), progression (B), and survival (C) in neuroblastoma patient dataset GEO: GSE49710 (n = 498). Transcription regulators in each group are highlighted in red dots and labeled on the plot. The x axis represents different regulons, whereas the y axis indicates rank for specific transcription regulators based on the regulon specificity scores.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Expressing, Labeling

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: Differential expression analysis distinguishes the expression pattern of oncogene-like and tumor-suppressor-like transcription regulator signatures in neuroblastoma patients The heatmap shows the stratification ability of differentially expressed transcription regulators in neuroblastoma patients (GEO: GSE49710 ; n = 498). Oncogene-like transcription regulators associated with high risk, death, disease progression, and stage 4 are shown in the red box (mean expression: 0.680). Tumor-suppressor-like transcription regulators are shown in the blue box of the bottom cluster (mean expression: −0.303). The labels on the right indicate transcription regulators as official gene symbols, whereas red and blue color coding represents higher and lower expression levels. Annotation tracks are given in the color key at the bottom of the heatmap, reporting neuroblastoma risk, survival, progression, and stages.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Expressing

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: Regulon specificity score analysis prioritizes SAP30 for association with mortality, disease progression, high risk, and stage 4 in neuroblastoma patients (A) The heatmap prioritizes transcription regulators based on the regulon specificity scores obtained from the neuroblastoma patient dataset GEO: GSE49710 (n = 498). The transcription regulators with high priority are given at the top, while low priority is given at the bottom. SAP30 has the highest priority score and is shown with a red arrow. The labels on the right indicate transcription regulators as official gene symbols, whereas red and blue color coding represent higher and lower regulon specificity score levels. Annotation tracks are given in the color key at the bottom of the heatmap, reporting neuroblastoma MYCN amplification status, age, sex, survival status, progression, risk, and stages. (B) The heatmap shows the regulon specificity score numbers and the prioritization of transcription regulators associated with different disease phenotypes obtained from the neuroblastoma patient dataset GEO: GSE49710 (n = 498). The transcription regulators with high priority are given at the top, while low priority is given at the bottom. SAP30 has the highest priority score and is shown with a red arrow. The labels on the right indicate transcription regulators as official gene symbols, whereas red and blue color coding represent a higher and lower expression of different regulons. Annotation tracks (aggregates [agg] and priority [pri]) are given at the bottom of the heatmap, reporting neuroblastoma disease phenotypes.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Amplification, Expressing

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: The distribution pattern of transcription regulators in neuroblastoma patients Violin plots show the distribution of transcription regulators expression in different stages of neuroblastoma, in patient datasets GEO: GSE45547 , n = 649 (A), and EMBL: E-MTAB-179 , n = 709 (C). The significance of the differences between different stage patients was determined by an unpaired t test (B and D).

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Expressing

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: SAP30 associates with high-risk status and poor survival in neuroblastoma patients (A and B) Immunofluorescence (A) and western blotting (B) image of SAP30 in low- and high-risk neuroblastoma patients (A), and MYCN -amplified, diagnosis- and progression-specific patient-derived xenograft (PDX) tumors (B). (C and D) Kaplan-Meier curves show the correlation between expression of SAP30 and overall survival (C) or event-free survival (D) from two independent patient datasets GEO: GSE49710 , n = 498 (left), and PMID: 32825087 , n = 786 (right). Patients with higher SAP30 had a shorter survival.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Immunofluorescence, Western Blot, Amplification, Derivative Assay, Expressing

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: Cisplatin resistant patient-derived xenograft tumors cells express higher SAP30 (A and B) Molecular surface (A) and schematic representation (B) of SAP30’s DNA domain, with residues (R, arginine; K, lysine; H, histidine) comprising the nucleolar localization sequence that mediate DNA binding highlighted. (C and D) CRISPR-Cas9 essentiality screen data of neuroblastoma cells show resistance to cisplatin (C) but sensitivity to BRD4 inhibitor drugs (D). (E) Western blotting image of SAP30 in two cisplatin-resistant neuroblastoma cells derived from patient-derived xenograft tumors.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Derivative Assay, Sequencing, Binding Assay, CRISPR, Western Blot

Journal: Molecular Therapy. Nucleic Acids

Article Title: SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma

doi: 10.1016/j.omtn.2022.03.014

Figure Lengend Snippet: SAP30 knockdown inhibits cell viability, induces cell death and mitochondrial membrane potential in neuroblastoma cells in vitro , and reduces tumor burden in vivo in a mouse xenograft model of neuroblastoma (A–D) A representative (A) western blotting image of SAP30 showing the knockdown efficiency, (B) quantification graph of cell viability assay evaluating the effect of SAP30 silencing on cell proliferation, and (C and D) flow cytometry pictures and quantification graphs of (C) cell death analysis and (D) mitochondrial membrane potential in neuroblastoma cells upon stable knockdown of SAP30 using two different shRNAs. (E and F) Tumor burden in (E) NOD/SCID mice receiving a subcutaneous injection of SK-N-B(E)2c cells with SAP30 stably silenced using two different shRNAs and (F) images of the excised tumors of the mice from various treatment groups are given. The data presented are the mean ± SD of three independent experiments. p values were calculated using two-tailed unpaired t tests between SAP30 knockdown and control cells. ∗p < 0.05.

Article Snippet: De-identified formalin-fixed and embedded paraffin blocks of neuroblastoma patient tissue microarray (no. NB642a) were obtained from US Biomax (26 patients’ samples, in duplicates).

Techniques: Membrane, In Vitro, In Vivo, Western Blot, Viability Assay, Flow Cytometry, Injection, Stable Transfection, Two Tailed Test