Journal: Molecular Cancer

Article Title: Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression

doi: 10.1186/s12943-024-02206-5

Figure Lengend Snippet: Quantitative proteomics characterization of VARS1 -overexpressing cell lines. ( A ) Volcano Plot representing the log 2 (Fold Change) vs. the -log 2 (p-value) for the VARS1 overexpression vs. control comparison. Differentially expressed proteins ( p < 0.1) are represented in blue (Hep3B) or pink (SNU-387). A Ven Diagram showing the total number of dysregulated proteins ( VARS1 overexpression vs. control) is provided together with the 20 commonly dysregulated proteins in both cell lines. ( B ) Reactome enrichment analyses for the differentially upregulated (red) and downregulated (green) proteins in Hep3B and SNU-387 VARS1 -overexpressing cells. ( C ) Heatmap representing the magnitude and significance of the changes in abundance (pVARS1 vs. Mock) of the 20 common VARS1-regulated proteins in Hep3B (top panel) and SNU-387 (bottom panel). Data are presented as mean ± standard error of the mean (SEM) from n = 3–5 independent experiments. ( D ) Correlations of VARS1 and MAGI1 levels in HCC patients (mRNA). ( E ) MAGI1 mRNA levels in VARS1 -silenced and VARS1 -overexpressing cells. ( F ) MAGI1 protein levels in VARS1 -silenced and VARS1 -overexpressing cells, measured by Western Blot. Asterisks indicate statistically significant differences (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001). Representative images of Western Blots for each condition and cell line are shown

Article Snippet: Importantly, MAGI1 has been shown to regulate the UPR in endothelial cells under inflammatory stimulus [ ], which lead us to hypothesize that MAGI1 could be part of the response caused by proteostasis alterations caused by VARS1 modulation.

Techniques: Quantitative Proteomics, Over Expression, Control, Comparison, Western Blot

Journal: Molecular Cancer

Article Title: Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression

doi: 10.1186/s12943-024-02206-5

Figure Lengend Snippet: VARS1 modulates MAGI1 expression to promote stemness and tumour establishment. ( A ) MAGI1 expression in HCC cohorts (mRNA and protein). ( B ) Proliferation, colonies, and tumorspheres formation assays on Hep3B and SNU-387 cell lines after MAGI1 overexpression. Representative images of colonies and tumorspheres after 10 days are shown for each condition and cell line. Data are presented as mean ± standard error of the mean (SEM) from n = 3–5 independent experiments. ( C ) Validation (mRNA and protein levels) of VARS1 alone and VARS1-MAGI1 simultaneous overexpression in cell lines. Representative images of Western Blots for each condition and cell line are shown. ( D ) Colonies and tumorspheres formation assays in VARS1 -overexpressing and VARS1-MAGI1 -overexpressing Hep3B (blue) and SNU-387 (yellow) cells. Representative images of colonies and tumorspheres formed after 10 days are depicted. Asterisks indicate statistically significant differences (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001). Data are presented as mean ± SEM from n = 3–5 independent experiments

Article Snippet: Importantly, MAGI1 has been shown to regulate the UPR in endothelial cells under inflammatory stimulus [ ], which lead us to hypothesize that MAGI1 could be part of the response caused by proteostasis alterations caused by VARS1 modulation.

Techniques: Expressing, Over Expression, Biomarker Discovery, Western Blot