Journal: Molecular Medicine Reports

Article Title: Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF-β signaling

doi: 10.3892/mmr.2019.10699

Figure Lengend Snippet: LINC01638 is significantly upregulated in tumor tissues than in adjacent healthy tissues in the majority of patients with PDAC (*P<0.05 tumor vs. healthy tissue). PDAC, pancreatic ductal adenocarcinoma.

Article Snippet: Human PDAC cell line PL45 (ATCC ® CRL-2558TM) and normal pancreas duct cell line hTERT-HPNE (ATCC ® CRL-4023TM) were purchased from the American Type Culture Collection (Manassas, VA, USA).

Techniques:

Journal: Molecular Medicine Reports

Article Title: Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF-β signaling

doi: 10.3892/mmr.2019.10699

Figure Lengend Snippet: Upregulation of plasma LINC01638 can distinguish patients with PDAC from healthy controls. (A) Plasma levels of LINC01638 were significantly higher in PDAC patients than in healthy controls and (B) upregulation of plasma LINC01638 distinguished PDAC patients from healthy controls in receiver operating characteristic (*P<0.05). PDAC, pancreatic ductal adenocarcinoma.

Article Snippet: Human PDAC cell line PL45 (ATCC ® CRL-2558TM) and normal pancreas duct cell line hTERT-HPNE (ATCC ® CRL-4023TM) were purchased from the American Type Culture Collection (Manassas, VA, USA).

Techniques: Clinical Proteomics

Journal: Molecular Medicine Reports

Article Title: Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF-β signaling

doi: 10.3892/mmr.2019.10699

Figure Lengend Snippet: Plasma levels of LINC01638 and TGF-β1 are positively correlated in patients with PDAC, and not in healthy controls. Pearson correlation analysis revealed a significant positive correlation between plasma levels of LINC01638 and TGF-β1 in (A) patients with PDAC and (B) healthy controls. PDAC, pancreatic ductal adenocarcinoma; TGF-β1, transforming growth factor-β1.

Article Snippet: Human PDAC cell line PL45 (ATCC ® CRL-2558TM) and normal pancreas duct cell line hTERT-HPNE (ATCC ® CRL-4023TM) were purchased from the American Type Culture Collection (Manassas, VA, USA).

Techniques: Clinical Proteomics

Journal: Molecular Medicine Reports

Article Title: Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF-β signaling

doi: 10.3892/mmr.2019.10699

Figure Lengend Snippet: LINC01638 regulates TGF-β1 expression in PDAC cells. (A) LINC01638 overexpression upregulated, (B) while LINC01638 shRNA downregulated the expression of TGF-β1 in cells of PDAC cell line, PL45, but not in the normal pancreas duct cell line hTERT-HPNE (*P<0.05). PDAC, pancreatic ductal adenocarcinoma; C, untransfected; NC, negative control (empty vector or NC shRNA transfection); TGF-β1, transforming growth factor-β1; shRNA, short hairpin RNA.

Article Snippet: Human PDAC cell line PL45 (ATCC ® CRL-2558TM) and normal pancreas duct cell line hTERT-HPNE (ATCC ® CRL-4023TM) were purchased from the American Type Culture Collection (Manassas, VA, USA).

Techniques: Expressing, Over Expression, shRNA, Negative Control, Plasmid Preparation, Transfection

Journal: Molecular Medicine Reports

Article Title: Downregulation of LINC01638 lncRNA inhibits migration and invasion of pancreatic ductal adenocarcinoma cells by reducing TGF-β signaling

doi: 10.3892/mmr.2019.10699

Figure Lengend Snippet: LINC01638 regulated PDAC cell migration and invasion through TGF-β1. Effects of LINC01638 overexpression, shRNA silencing and exogenous TGF-β1 treatment on (A) migration and (B) invasion of PL45 human PDAC cell line and hTERT-HPNE normal pancreas duct cell line. *P<0.05. Magnification, ×40. PDAC, pancreatic ductal adenocarcinoma; C, untransfected; NC, negative control (empty vector transfection); shRNA, short hairpin RNA; TGF-β1, transforming growth factor-β1.

Article Snippet: Human PDAC cell line PL45 (ATCC ® CRL-2558TM) and normal pancreas duct cell line hTERT-HPNE (ATCC ® CRL-4023TM) were purchased from the American Type Culture Collection (Manassas, VA, USA).

Techniques: Migration, Over Expression, shRNA, Negative Control, Plasmid Preparation, Transfection

Journal: Signal Transduction and Targeted Therapy

Article Title: Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-025-02546-8

Figure Lengend Snippet: Metabolic Gene Expression Highlights Functional and Cellular Heterogeneity in PDAC. a UMAP plot showing PDAC and normal pancreatic cells clustered for whole gene expression (above) and metabolic genes (below). b Dot plot of representative marker genes for each cell cluster. Color intensity reflects the relative expression of the gene, while size is proportionate to the fraction of cells expressing a given gene. c Upset plot of intersection for cell type attribution, reference paper, metabolic genes, and whole gene expression. d Statistically significant results from GO analysis for biological processes in normal and tumor ductal cells. e Log 2 -normalized expression values of the glycolytic gene signature across tumor ductal cells. Patients were stratified into High (red) and Low (light blue) glycolysis groups based on the median glycolytic signature score. The red dashed line indicates the mean expression within the cohort. f Volcano plot showing genes differentially expressed between the High and Low glycolysis groups. Red and light-blue dots indicate genes significantly upregulated in the High and Low groups, respectively. The x - and y -axes represent log₂ fold change and −log 10 p value, respectively. g Gene Ontology (GO) enrichment analysis of genes upregulated in the High and Low groups. Pathways associated with “glycolysis” and “positive regulation of glycolytic process” are highlighted. The x -axis represents transformed significance (−log 10 p value), and dot size indicates the odds gene ratio. h GSEA enrichment plot for the Hallmark Glycolysis pathway comparing High and Low groups, showing significant enrichment of glycolytic genes in the High-glycolysis samples

Article Snippet: Fig. 4 Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR).

Techniques: Gene Expression, Functional Assay, Marker, Expressing, Transformation Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-025-02546-8

Figure Lengend Snippet: Spatial Profiling Uncovers Glycolytic Signatures and TME Heterogeneity in PDAC. a PDAC patient samples stained for INS + , GCG + , PanCK − and PanCK + markers and processed for spatial transcriptomics. White squares highlight areas of interest for gene expression acquisition. Colored bords refer to marker positivity INS + (orange), GCG + (green), PanCK − (light blue), and PanCK + (purple). b Histograms of deconvoluted spatial transcriptomics data displaying TME cell type percentage in PDAC patients, stratified for tumor stage. c Modules of gene expression across cell types highlight highly expressed genes in tumor cells, along with Gene Ontology (GO) analysis displaying statistically significant biological processes. Label below each cluster refers to marker positivity INS + (orange), GCG + (green), PanCK − (light blue), and PanCK + (purple). d Circos plot of glucose-related activity derived GO analysis. e Heatmap depicting glycolytic signature expression in PDAC patients, with two Areas of Interest (AOIs) per patient, resulting in two rows for each patient. Data are represented as mean ± SD

Article Snippet: Fig. 4 Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR).

Techniques: Staining, Gene Expression, Marker, Activity Assay, Derivative Assay, Expressing

Journal: Signal Transduction and Targeted Therapy

Article Title: Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-025-02546-8

Figure Lengend Snippet: Glycolytic Signature Defines Prognostic Subgroups and Functional Associations in PDAC. a Pairwise correlation for gene expression in the TCGA cohort of PDAC patients. b Heatmap for unsupervised clustering analysis with glycolytic signature expression in the TCGA cohort of PDAC patients. c TCGA-PDAC cohort divided in tertile and grouped in High, Intermediate, and Low based on glycolytic signature expression (above). Glycolytic enrichment was compared between High vs Intermediate, and High vs Low group, and between Intermediate vs Lowest group. The y -axis represents the normalized enrichment score with statistical significance indicated by p value: <0.0001 ****, <0.001 ** (below). Data are represented as mean ± SD. d Kaplan–Meier plot showing 3-year overall survival across glycolytic groups in the TCGA cohort of PDAC patients. e Association and distribution of glycolytic groups with KRAS mutational status, hypoxia score, Basal-like/Classical molecular subtype, tumor purity, and tumor stage across the TCGA and independent validation cohorts of PDAC patients (top). Each dot represents the statistical significance of the association between the glycolytic group and the indicated clinical or molecular variable, evaluated using either Fisher’s exact test or the Chi-squared test (bottom). The red dashed line indicates the significance threshold ( p = 0.05)

Article Snippet: Fig. 4 Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR).

Techniques: Functional Assay, Gene Expression, Expressing, Biomarker Discovery

Journal: Signal Transduction and Targeted Therapy

Article Title: Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-025-02546-8

Figure Lengend Snippet: Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR). Each dot represents a biological replicate ( n = 6 per group). Data are represented as mean ± SD. Statistical analysis performed with a paired t -test. d Viability assay in MIAPaCa-2 (green), PANC-1 (blue), PL45 (purple), HPAF-II (red), and HPDE6c7 (brown) cells upon LDHA-i treatment at 24 and 48 h. Boxplots display IC50 values for each time point across cell lines, with statistical significance assessed by paired t -test ( n = 2 per group). On the right, GR50 and GRmax values represent drug potency and efficacy, respectively

Article Snippet: Fig. 4 Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR).

Techniques: Inhibition, Expressing, Western Blot, Activity Assay, Viability Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: Glycolytic heterogeneity drives metabolic-targeted therapy in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-025-02546-8

Figure Lengend Snippet: Metabolomic, Proteomic, and Transcriptomic Profiling Uncovers the Impact of LDHA Inhibition in PDAC. a Amount of lactate in MIAPaCa-2 and PL45 cells at the basal level (gray) and after LDHA inhibition (blue). Each dot represents a biological replicate ( n = 6 per group). Data are shown as normalized intensity and are represented as mean ± SD. Statistical significance was calculated with a paired t -test. b Pathway enrichment analysis performed on metabolomics data in MIAPaCa-2 cells at basal level and after LDHA inhibition. The x -axis indicates pathway impact based on metabolite expression. The y -axis indicates p value transformed as −Log 10 . c Significant results from enrichment analysis performed on proteomics data in MIAPaCa-2 cells after LDHA inhibition. The x -axis indicates the normalized enrichment score. The label shows p value transformed as −Log 10 . d Enrichment plots for glycolysis and hypoxia in MIAPaCa-2 cells treated with LDHA-i. Normalized enrichment score and p value are reported in the figure. e Hallmarks significantly upregulated in PDAC patient samples exhibiting High glycolytic profile compared to those with Low glycolytic profile (left). Hallmarks significantly downregulated in MIAPaCa-2 cells following treatment with LDHA-i (right). The y -axis indicates the normalized enrichment score

Article Snippet: Fig. 4 Glycolytic Profiling and LDHA Inhibition Reveal Differential Sensitivity Across PDAC Cell Lines. a Heatmap of glycolytic signature expression, reported as normalized transcript per million (nTPM) across five PDAC cell lines from Human Protein Atlas. b Western blot analysis of LDHA expression in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells. c Glycolytic activity in PL45, SW1990, PANC-1, MIAPaCa-2, and HPAF-II cells after LDHA-i treatment, measured as extracellular acidification rate (ECAR).

Techniques: Metabolomic, Inhibition, Expressing, Transformation Assay