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Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: Prognostic significance and cellular functional states of SERPINE1. (A) Heatmap of survival (GEPIA2) showing the HRs for SERPINE1 expression across type of cancers (expression data and clinical survival data are sourced from The Cancer Genome Atlas projects. The cohort was split into two groups based on the expression level of SERPINE1. GEPIA2 employs a quartile-based cut-off: tumors with SERPINE1 expression levels at or above the 75th percentile are classified into the 'high expression' group, and those with SERPINE1 expression at or below the 25th percentile are classified into the 'low expression' group. This method minimizes the effects of outliers. Red and blue indicate higher and lower risks, respectively; highlighted boxes denote significant outcomes (P<0.05). (B) Kaplan-Meier curves for the significance of the effect of SERPINE1 on overall survival. The statistical significance of the difference between survival curves was computed using the log-rank (Mantel-Cox) test. The analysis outputs HR with its confidence interval and the log-rank P-value, all of which are annotated in the figure. (C) SERPINE1 expression in BRCA, LGG, and SKCM tumors compared with normal tissues (GEPIA2). For BRCA, there were 1,085 tumor samples and 291 normal samples; for LGG, 518 tumor samples and 207 normal samples; and for SKCM, 461 tumor samples and 558 normal samples. (D) Average correlation of SERPINE1 expression with functional states in cancers (CancerSEA database). Correlations with an absolute Spearman's ρ>0.3 and a Benjamini and Hochberg adjusted P-value (false discovery rate) <0.05 were considered significant. * P<0.05. SERPINE1, serine protease inhibitor clade e member 1; GEPIA2, gene expression profiling interactive analysis 2; HR, hazard ratio; BRCA, breast cancer; LGG, low-grade glioma; SKCM, skin cutaneous melanoma.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: Functional Assay, Expressing, Protease Inhibitor, Gene Expression
Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: Diverse effects of SERPINE1 knockdown on cell proliferation. (A) Western blotting showing SERPINE1 protein levels in 231, H4, and C918 cells following transfection with the shSE1 and shc with GAPDH serving as the loading control. Band intensities were measured using ImageJ software and are presented as ratios. These ratios were calculated as (target protein/GAPDH levels) in the experimental group divided by those in the control group. Data represent mean ± SDs of three independent experiments. (B) Colony formation ability of shSE1 and control (shc) cells. Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs of three independent experiments. (C-D) Xenograft tumors derived from (C) 231 and (D) C918 cells with shSE1 and shc cells; the tumor growth and weight were compared between shSE1 and shc groups. Statistical significance was determined using two-way ANOVA followed by Šídák's multiple comparisons test (tumor growth) and a two-sided Student's t test (tumor weight). The data are presented as the means ± SDs. n=5. (E-F) Lung metastatic foci in nude mice were stained with H&E and GFP (scale bar, 100 μ m). The fractions (numerator/denominator) adjacent to the images represent the lung metastatic focus rate (defined as the number of mice with lung metastases per total number of injected mice). The lung metastatic focus rate was: 4 of 6 for 231-shSE1 versus 5 of 6 for 231-shc; and 6 of 6 for both C918-shSE1 and C918-shc. Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs. n=6. *** P<0.001, ** P<0.01. SERPINE1, serine protease inhibitor clade e member 1; shRNA, short hairpin RNA; shSE1, shRNA targeting SERPINE1; shc, shRNA scrambled control; H&E, hematoxylin and eosin staining; GFP, green fluorescent protein.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: Knockdown, Western Blot, Transfection, Control, Software, Derivative Assay, Staining, Injection, Protease Inhibitor, shRNA
Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: SERPINE1-mediated cell cycle regulation. (A) The GO enrichment analysis of DEGs obtained from RNA-seq revealed significant changes in biological processes after SERPINE1 knockdown between shSE1 and shc groups across three cell lines. RNA-seq was performed using one biological replicate per group. (B) Heatmap of DEGs associated with the highlighted processes in (A). (C) Western blotting was performed on nuclear and cytoplasmic extracts to detect MCM3 and p-MCM3 levels (histone H3 and GAPDH were used as controls). The relative levels of p-MCM3 and MCM3 were normalized to the expression of histone H3 and GAPDH, respectively. The relative p-MCM3/MCM3 ratio was subsequently calculated. Data represent mean ± SDs of three independent experiments. (D) Flow cytometry of the cell cycle phase distribution (G 0 /G 1 , S, and G 2 /M phases). Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs of three independent experiments. (E) Scatter plot of 89 cycle regulators from the protein array, highlighting SMAD3 and TP53. Blue indicates downregulated proteins (fold change ≥1.2); red indicates upregulated proteins (fold change ≤0.83); and grey indicates no change in the protein level. n=4 (F) RNA-seq data showing changes in the indicated gene expression between shSE1 and shc groups across three cell lines. RNA-seq was performed using one biological replicate per group. (G) Western blotting of the indicated proteins in C918 cells (shSE1 vs. shc). The ratios indicate the relative changes in the expression levels of the indicated proteins. Data represent mean ± SDs of three independent experiments. * P<0.05; ns, not significant. SERPINE1, serine protease inhibitor clade e member 1; GO, Gene Ontology; DEGs, differentially expressed genes; RNA-seq, RNA sequencing; shRNA, short hairpin RNA; shSE1, shRNA targeting SERPINE1; shc, shRNA scrambled control; FDR, false discovery rate; p-, phosphorylated.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: RNA Sequencing, Knockdown, Western Blot, Expressing, Flow Cytometry, Protein Array, Gene Expression, Protease Inhibitor, shRNA, Control
Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: SERPINE1-mediated modulation of the ERK/p38 ratio and anoikis. (A) Upper panel: western blotting showing ERK, p-ERK, p38, and p-p38 levels. Quantitative data showed the p-ERK/ERK and p-p38/p38 ratios in SERPINE1 knockdown cells compared with control cells. Lower panel: western blotting analysis of p-AKT, AKT, p-JNK and JNK (normalized to total protein) levels in the shSE1 and shc groups. The numbers beneath the bands represent the ratios of the expression levels of the indicated proteins. Data represent mean ± SDs of three independent experiments. (B) PLAUR and HSP90AA1 mRNA and protein levels in shSE1 and shc cells analyzed using RNA-seq (left panel) and western blotting (right panel). The numbers beneath the bands represent the ratios of the expression levels of the indicated proteins and represent mean ± SDs of three independent experiments. RNA-seq was performed using one biological replicate per group. (C-D) Upper panel: (C) 231-shSE1 cells were infected with lentivirus containing PLAUR cDNA (ex-PLAUR) or the corresponding empty vector control (vec). (D) H4-shSE1 cells were transfected with siRNA targeting HSP90AA1 (si-HSP90AA1) or siNC. The expression levels of uPAR and HSP90α, as well as the activity of ERK and p38, were detected by western blotting, with GAPDH serving as the loading control. Data represent mean ± SDs of three independent experiments. Lower panel: Cell proliferation was assessed by CCK-8 assay in 231-shSE1 cells infected with ex-PLAUR or vec, and in H4-shSE1 cells transfected with si-HSP90AA1 or siNC. Statistical significance was determined using two-way ANOVA followed by Šídák's multiple comparisons test. The data are presented as the means ± SDs. n=6. (E) Morphology of shSE1 and shc cells cultured under suspension condition. (scale bar, 100 μ m). (F) Apoptotic cells cultured under suspension condition were analyzed by flow cytometry following Annexin V-PE/7AAD staining (72 h of suspension culture). Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs of three independent experiments. ** P<0.01 *** P<0.001, ns, not significant. SERPINE1, serine protease inhibitor clade e member 1; p-, phosphorylated; shRNA, short hairpin RNA; shSE1, shRNA targeting SERPINE1; shc, shRNA scrambled control; PLAUR, plasminogen activator, urokinase receptor; HSP90AA1, heat shock protein 90 alpha family class a member 1; RNA-seq, RNA sequencing; vec, empty vector control; siRNA, short interfering RNA; siNC, negative control siRNA; uPAR, urokinase-type plasminogen activator receptor; HSP90α, heat shock protein 90-alpha.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: Western Blot, Knockdown, Control, Expressing, RNA Sequencing, Infection, Plasmid Preparation, Transfection, Activity Assay, CCK-8 Assay, Cell Culture, Suspension, Flow Cytometry, Staining, Protease Inhibitor, shRNA, Small Interfering RNA, Negative Control
Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: Variable effects of SERPINE1 on cell migration and invasion. (A) KEGG enrichment analysis via GSEA comparing high and low SERPINE1 expression in BRCA, LGG, and SKCM (TCGA dataset). Representative images and quantification of Transwell assays of the migration (B) of shSE1 and shc cells. Representative images and quantification of Transwell invasion assays through (C) Matrigel and (D) collagen type I. Cells from three random fields in triplicate wells were counted. Scale bar, 100 μ m. Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs of three independent experiments. ** P<0.01, * P<0.05. SERPINE1, serine protease inhibitor clade e member 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSEA, gene set enrichment analysis; BRCA, breast cancer; LGG, low-grade glioma; SKCM, skin cutaneous melanoma; TCGA, The Cancer Genome Atlas; NES, normalized enrichment score; FDR, false discovery rate.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: Migration, Expressing, Protease Inhibitor
Journal: International Journal of Oncology
Article Title: Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
doi: 10.3892/ijo.2026.5871
Figure Lengend Snippet: SERPINE1 regulates MMP activity. (A) MMP and TIMP levels in the supernatants of shSE1 and shc cells after 24 h of incubation and 10-fold concentration. Statistical significance was determined using a two-sided Student's t test. The data are presented as the means ± SDs. n=4. (B) Quantification of active MMP-1 and MMP-13 levels in cell lysates using fluorescence ELISA. Statistical significance was determined using two-way ANOVA followed by Šídák's multiple comparisons test. The data are presented as the means ± SDs of three independent experiments. (C) Western blotting showing the levels of the indicated proteins in H4-shSE1 cells at 72 h after transfection with the si-HSP90AA1 or siNC. The numbers beneath the bands represent the ratios of the expression levels of the indicated proteins and represent mean ± SDs of three independent experiments. (D) Representative images and quantification of Transwell invasion assays through Matrigel and collagen type I in H4-shSE1 cells transfected with the si-HSP90AA1 or siNC (scale bar, 100 μ m). Statistical significance was determined using a two-sided Student's t-test. The data are presented as the means ± SDs of three independent experiments. (E) Diagram showing the mechanisms underlying the effects of SERPINE1 on cancer proliferation and invasion. SERPINE1 knockdown influences cell proliferation and invasion through distinct signaling pathways. With respect to proliferation, SERPINE1 knockdown reduces TGF-β levels, and this reduction alters the activity of SMAD3, p53, and MCM3 to promote cell cycle progression. SERPINE1 knockdown interferes with the uPAR-mediated balance of the ERK/p38 ratio; it may also affect this ratio by modulating HSP90α expression and p38 activity, which suppress cell proliferation. In terms of invasion, SERPINE1 downregulation increases MMP-1 levels via the HSP90α-p38 pathway, thereby promoting cellular invasion. *** P<0.001, ** P<0.01, ns, not significant. SERPINE1, serine protease inhibitor clade e member 1; MMP, matrix metalloproteinases; TIMP, tissue inhibitors of metal proteases; shRNA, short hairpin RNA; shSE1, shRNA targeting SERPINE1; si, short interfering RNA; siHSP90AA1, short interfering heat shock protein 90 alpha family class a member 1; NC, negative control; uPAR, urokinase-type plasminogen activator receptor; p-, phosphorylated; MCM3, minichromosome maintenance complex component 3; HSP90α, heat shock protein 90-alpha.
Article Snippet: The concentration of SERPINE1 in the cell culture supernatant was measured using a
Techniques: Activity Assay, Incubation, Concentration Assay, Fluorescence, Enzyme-linked Immunosorbent Assay, Western Blot, Transfection, Expressing, Knockdown, Protein-Protein interactions, Protease Inhibitor, shRNA, Small Interfering RNA, Negative Control
Journal: BMC Microbiology
Article Title: Reproductive tract microbiota dysbiosis in ovarian endometrioma and adenomyosis: multi-site 16S rRNA profiling and functional impact of key bacterial species on human endometrial stromal cells
doi: 10.1186/s12866-025-04412-7
Figure Lengend Snippet: Validation of key differentially expressed genes (DEGs) at mRNA and protein levels. A-B qRT-PCR validation of relative mRNA expression levels for selected genes (CEBPB, SERPINE1, S100A1, CKS1B, ADH1B, MYOM1, PTGFR, ACLY) in T-HESCs comparing AM vs. NC and CC vs. NC co-culture conditions. Expression normalized to GAPDH. C-D ELISA validation of protein concentrations for corresponding key molecules in cell culture supernatants, comparing AM vs. NC and CC vs. NC co-culture conditions. Data presented as mean ± SD or similar; significance indicated ( P < 0.05)
Article Snippet: Kits used included those for: ADH1B (MyBioSource, Cat. No. MBS4503934); MYOM1 (Thermo Fisher Scientific, Cat. No. PIPA5100626; or Proteintech, Cat. No. 22084-1-AP); PTGFR (ABclonal, Cat. No. RK07240; or MyBioSource, Cat. No. MBS9714736); ACLY (RayBiotech, Cat. No. ELH-ACLY; Biomatik, Cat. No. EKF60626 ; BPS Bioscience, Cat. No. 79904; or ABclonal, Cat. No. RK12483); CEBPB (Antibodies-online, Cat. No. ABIN989871);
Techniques: Biomarker Discovery, Quantitative RT-PCR, Expressing, Co-Culture Assay, Enzyme-linked Immunosorbent Assay, Cell Culture
Figure S6 and Journal: Cell Reports Medicine
Article Title: A spatially resolved transcriptome landscape during thyroid cancer progression
doi: 10.1016/j.xcrm.2025.102043
Figure Lengend Snippet: Cell-cell communications in thyroid cancer (A) Bubble plot illustrating the spatial correlations of dysregulated ligand-receptor pairs between PTC, LPTC, or ATC and PT samples in the ST data. (B and C) Bar plots showing fold changes in ligand (B) and receptor (C) expression in PTC, LPTC, and ATC samples compared to PT samples. (D) Spatial feature plots highlighting SERPINE1 (ligand) and PLAUR (receptor) expression in representative samples (PT-2, PTC-2, LPTC-2, and ATC-3). (E and F) Expression levels of SERPINE1 (E) and PLAUR (F) across various cell types. (G) SERPINE1 expression within fibroblasts, with the inset indicating enrichment of fibroblast subpopulations stratified by SERPINE1 expression levels. (H) PLAUR expression within macrophages, with the inset showing enrichment of macrophage subpopulations stratified by PLAUR expression levels. (I) Multiplex immunofluorescence staining for Fib-12 fibroblast markers ( CXCL8 , CXCL1 , and SERPINE1 ) and Mac-11 macrophages ( CXCL12 , STAB1 , and PLAUR ) in PTC, LPTC, and ATC samples. Scale bar: 40 μm. (J) Boxplot comparing SERPINE1 expression in cancer ( n = 58) versus paired NAT ( n = 58) samples from the TCGA thyroid carcinoma (THCA) cohort. (K) Kaplan-Meier survival curve from the TCGA THCA cohort ( n = 510) showing patient survival based on median SERPINE1 expression levels. See also
Article Snippet:
Techniques: Expressing, Multiplex Assay, Immunofluorescence, Staining
Journal: Cell Reports Medicine
Article Title: A spatially resolved transcriptome landscape during thyroid cancer progression
doi: 10.1016/j.xcrm.2025.102043
Figure Lengend Snippet:
Article Snippet:
Techniques: Recombinant, Software
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: The relationship between SERPINE1 expression and prognosis. (A) SERPINE1 gene expression in HNSCC and normal tissues (TCGA); (B) SERPINE1 gene expression in HNSCC and adjacent cancer tissues (TCGA); (C) Impact of SERPINE1 gene expression on OS (TCGA); (D) impact of SERPINE1 gene expression on DSS (TCGA); (E) impact of SERPINE1 gene expression on OS (GSE41613); (F) Impact of SERPINE1 gene expression on DSS (GSE41613); (G) Impact of SERPINE1 gene expression on OS (GSE65858); (H) Impact of SERPINE1 gene expression on PFS (GSE65858). * p < 0.05, ** p < 0.01 and *** p < 0.001.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Expressing, Gene Expression
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: The association between SERPINE1 and clinical features. (A, B) The relationship between HPV status and SERPINE1 expression (TCGA and GSE65858 data) * p < 0.05, ** p < 0.01, *** p < 0.001.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Expressing
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: Visualization of Enriched Pathways. (A) Volcano plot illustrating the differential expression of genes between HNSCC and normal tissues; (B) GO and KEGG analyses highlighting SERPINE1 and genes with low expression; (C, D) GSEA showing enrichment analysis of SERPINE1.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Quantitative Proteomics, Expressing
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: Protein–protein interaction between SERPINE1 and related genes.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques:
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: The impact of SERPINE1 on immune cells and the microenvironment. (A) 12 types of immune cells significantly affected by SERPINE1 expression; (B) the relationship between SERPINE1 and immune‐related scores. * p < 0.05, ** p < 0.01, *** p < 0.001.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Expressing
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: SNV, CNV, and methylation of SERPINE1 and their prognosis. (A, B) SNV of SERPINE1; (C, D) CNV of SERPINE1; (E, F) methylation of SERPINE1; (G–J) the relationship between SERPINE1 expression and survival period.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Methylation, Expressing
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: Drugs and SERPINE1 expression in CTRP and GDSC. (A) CTRP and GDSC both show drugs that are associated with SERPINE1; (B) The top three drugs with positive and negative correlation coefficients with SERPINE1 expression in CTRP and GDSC; (C) CTRP and GSDC show the commonly used chemotherapy drugs for HNSCC associated with SERPINE1.
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Expressing
Journal: Cancer Medicine
Article Title: Prognostic Significance and Therapeutic Potential of SERPINE1 in Head and Neck Squamous Cell Carcinoma
doi: 10.1002/cam4.70605
Figure Lengend Snippet: Immunohistochemistry: High expression of SERPINE1 in HNSCC. (A) The immunohistochemical scoring of SERPINE1 in the chip and the correlation between the scoring and clinical indices (* p < 0.05, ** p < 0.01, *** p < 0.001); (B) Immunohistochemical staining of SERPINE1 in tumor and adjacent cancer tissues shows strong tumor positivity; (C) positive of tumor; (D) negative of tumor; (E) negative of adjacent tissue (CHIP, the scale above is 200 μm, the scale below is 50 μm).
Article Snippet: Sections were then incubated overnight at 4°C with a primary
Techniques: Immunohistochemistry, Expressing, Immunohistochemical staining, Staining