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Graphical abstract. Graphical abstract illustrating the hypothetical mechanism by which JMJD6 promotes tumor progression and immune evasion in GC. JMJD6 is overexpressed in gastric cancer cells and promotes <t>BRD4</t> expression, which upregulates IRF1 and consequently increases PD-L1 expression. Elevated PD-L1 expression on tumor cells inhibits T cell–mediated antitumor immunity, thereby facilitating immune escape.
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Graphical abstract. Graphical abstract illustrating the hypothetical mechanism by which JMJD6 promotes tumor progression and immune evasion in GC. JMJD6 is overexpressed in gastric cancer cells and promotes <t>BRD4</t> expression, which upregulates IRF1 and consequently increases PD-L1 expression. Elevated PD-L1 expression on tumor cells inhibits T cell–mediated antitumor immunity, thereby facilitating immune escape.
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Graphical abstract. Graphical abstract illustrating the hypothetical mechanism by which JMJD6 promotes tumor progression and immune evasion in GC. JMJD6 is overexpressed in gastric cancer cells and promotes <t>BRD4</t> expression, which upregulates IRF1 and consequently increases PD-L1 expression. Elevated PD-L1 expression on tumor cells inhibits T cell–mediated antitumor immunity, thereby facilitating immune escape.
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Phenome-wide association study (PheWAS) analysis of genetic variations in strong candidate genes regulated by Arrb2 . Scatter plots show the PheWAS results for ( A ) Dnmt3a , ( B ) Myh9 , ( C ) Ccdc88a , ( D ) Dnmt1 , ( E ) Becn1 , ( F ) Gng2 , ( G ) Psmb6 , and ( H ) <t>Brd4</t> . Each scatter represents a phenotype, and the x -axis coordinates of the scatter are randomly distributed. The y -axis represents the association significance between each gene and central nervous system-related traits in BXD mice, with the red dotted line marking the statistical significance threshold (–log10( p ) = 3).
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Phenome-wide association study (PheWAS) analysis of genetic variations in strong candidate genes regulated by Arrb2 . Scatter plots show the PheWAS results for ( A ) Dnmt3a , ( B ) Myh9 , ( C ) Ccdc88a , ( D ) Dnmt1 , ( E ) Becn1 , ( F ) Gng2 , ( G ) Psmb6 , and ( H ) <t>Brd4</t> . Each scatter represents a phenotype, and the x -axis coordinates of the scatter are randomly distributed. The y -axis represents the association significance between each gene and central nervous system-related traits in BXD mice, with the red dotted line marking the statistical significance threshold (–log10( p ) = 3).
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Phenome-wide association study (PheWAS) analysis of genetic variations in strong candidate genes regulated by Arrb2 . Scatter plots show the PheWAS results for ( A ) Dnmt3a , ( B ) Myh9 , ( C ) Ccdc88a , ( D ) Dnmt1 , ( E ) Becn1 , ( F ) Gng2 , ( G ) Psmb6 , and ( H ) <t>Brd4</t> . Each scatter represents a phenotype, and the x -axis coordinates of the scatter are randomly distributed. The y -axis represents the association significance between each gene and central nervous system-related traits in BXD mice, with the red dotted line marking the statistical significance threshold (–log10( p ) = 3).
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Graphical abstract. Graphical abstract illustrating the hypothetical mechanism by which JMJD6 promotes tumor progression and immune evasion in GC. JMJD6 is overexpressed in gastric cancer cells and promotes BRD4 expression, which upregulates IRF1 and consequently increases PD-L1 expression. Elevated PD-L1 expression on tumor cells inhibits T cell–mediated antitumor immunity, thereby facilitating immune escape.

Journal: Scientific Reports

Article Title: Overexpression of JMJD6 drives immune evasion via the BRD4–IRF1–PD-L1 axis and promotes malignancy in gastric cancer

doi: 10.1038/s41598-025-30705-y

Figure Lengend Snippet: Graphical abstract. Graphical abstract illustrating the hypothetical mechanism by which JMJD6 promotes tumor progression and immune evasion in GC. JMJD6 is overexpressed in gastric cancer cells and promotes BRD4 expression, which upregulates IRF1 and consequently increases PD-L1 expression. Elevated PD-L1 expression on tumor cells inhibits T cell–mediated antitumor immunity, thereby facilitating immune escape.

Article Snippet: Anti-JMJD6 mouse monoclonal antibody (sc-28348; Santa Cruz Biotechnology, TX, USA), anti-PD-L1 rabbit monoclonal antibody (13684; Cell Signaling Technology, MA, USA), anti-ACTB rabbit monoclonal antibody (3700; Cell Signaling Technology), anti-BRD4 rabbit polyclonal antibody (A301-985A50; Bethyl Laboratories, TX, USA), and anti-IRF1 rabbit monoclonal antibody (8478; Cell Signaling Technology) were used.

Techniques: Expressing

JMJD6 regulates BRD4, IRF1 and PD-L1 expression. ( a ) The knockdown of JMJD6 by transfection with siRNA-JMJD6 suppressed BRD4, IRF1 and PD-L1 in MKN74. In addition, the knockdown of BRD4 by transfection with siRNA-BRD4 suppressed IRF1 and PD-L1 in MKN74. In contrast, the knockdown of BRD4 did not suppress JMJD6 in MKN74. ( b ) Knockdown of JMJD6 suppressed PD-L1 and BRD4 expression in MKN74 gastric cancer (GC) cells. White dotted lines indicate nuclear boundaries. ( c ) Co-culture assay of GC cells and T cells. Under JMJD6 knockdown, T cells had more potent anti-tumor activity against GC cells compared with NC, and the proliferation ratio of GC cells was significantly decreased (mean ± SD, n = 3; error bars indicate SD, n = 3). ( d ) An impedance-based tumor-cell killing assay. The knockdown of JMJD6 increased the anti-tumor activity of T cells and inhibited the proliferation of GC cells. ( e ) JMJD6 overexpression using plasmid transfection promotes BRD4, IRF1 and PD-L1 expression. ( f ) A hypothetical model of the overexpression or activation of JMJD6 in GC cells.

Journal: Scientific Reports

Article Title: Overexpression of JMJD6 drives immune evasion via the BRD4–IRF1–PD-L1 axis and promotes malignancy in gastric cancer

doi: 10.1038/s41598-025-30705-y

Figure Lengend Snippet: JMJD6 regulates BRD4, IRF1 and PD-L1 expression. ( a ) The knockdown of JMJD6 by transfection with siRNA-JMJD6 suppressed BRD4, IRF1 and PD-L1 in MKN74. In addition, the knockdown of BRD4 by transfection with siRNA-BRD4 suppressed IRF1 and PD-L1 in MKN74. In contrast, the knockdown of BRD4 did not suppress JMJD6 in MKN74. ( b ) Knockdown of JMJD6 suppressed PD-L1 and BRD4 expression in MKN74 gastric cancer (GC) cells. White dotted lines indicate nuclear boundaries. ( c ) Co-culture assay of GC cells and T cells. Under JMJD6 knockdown, T cells had more potent anti-tumor activity against GC cells compared with NC, and the proliferation ratio of GC cells was significantly decreased (mean ± SD, n = 3; error bars indicate SD, n = 3). ( d ) An impedance-based tumor-cell killing assay. The knockdown of JMJD6 increased the anti-tumor activity of T cells and inhibited the proliferation of GC cells. ( e ) JMJD6 overexpression using plasmid transfection promotes BRD4, IRF1 and PD-L1 expression. ( f ) A hypothetical model of the overexpression or activation of JMJD6 in GC cells.

Article Snippet: Anti-JMJD6 mouse monoclonal antibody (sc-28348; Santa Cruz Biotechnology, TX, USA), anti-PD-L1 rabbit monoclonal antibody (13684; Cell Signaling Technology, MA, USA), anti-ACTB rabbit monoclonal antibody (3700; Cell Signaling Technology), anti-BRD4 rabbit polyclonal antibody (A301-985A50; Bethyl Laboratories, TX, USA), and anti-IRF1 rabbit monoclonal antibody (8478; Cell Signaling Technology) were used.

Techniques: Expressing, Knockdown, Transfection, Co-culture Assay, Activity Assay, Over Expression, Plasmid Preparation, Activation Assay

Phenome-wide association study (PheWAS) analysis of genetic variations in strong candidate genes regulated by Arrb2 . Scatter plots show the PheWAS results for ( A ) Dnmt3a , ( B ) Myh9 , ( C ) Ccdc88a , ( D ) Dnmt1 , ( E ) Becn1 , ( F ) Gng2 , ( G ) Psmb6 , and ( H ) Brd4 . Each scatter represents a phenotype, and the x -axis coordinates of the scatter are randomly distributed. The y -axis represents the association significance between each gene and central nervous system-related traits in BXD mice, with the red dotted line marking the statistical significance threshold (–log10( p ) = 3).

Journal: Genes

Article Title: Systems Genetics Reveals the Gene Regulatory Mechanisms of Arrb2 in the Development of Autism Spectrum Disorders

doi: 10.3390/genes16050605

Figure Lengend Snippet: Phenome-wide association study (PheWAS) analysis of genetic variations in strong candidate genes regulated by Arrb2 . Scatter plots show the PheWAS results for ( A ) Dnmt3a , ( B ) Myh9 , ( C ) Ccdc88a , ( D ) Dnmt1 , ( E ) Becn1 , ( F ) Gng2 , ( G ) Psmb6 , and ( H ) Brd4 . Each scatter represents a phenotype, and the x -axis coordinates of the scatter are randomly distributed. The y -axis represents the association significance between each gene and central nervous system-related traits in BXD mice, with the red dotted line marking the statistical significance threshold (–log10( p ) = 3).

Article Snippet: The PVDF membrane was incubated at 4 °C overnight with primary antibodies, including mouse anti GAPDH (HRP-conjugated, 1:10,000, Proteintech, 60,004, Wuhan, Hubei, China), rabbit anti β-Arrestin2 (1:1000, Cell Signaling Technology, 3857, Danvers, Massachusetts, USA), rabbit anti Dnmt1 (1:2000, HuaBio, ET1702-77, Hangzhou, Zhejiang, China), rabbit anti Myh9 (1:2000, Abclonal, A0173, Wuhan, Hubei, China), rabbit anti Brd4 (1:1000, HuaBio, HA722785, Hangzhou, Zhejiang, China), rabbit anti p-Synapsin I (S9) (1:1000, HuaBio, ET1611-26, Hangzhou, Zhejiang, China), rabbit anti Synapsin I (1:1000, abcam, ab64581, Cambridge, UK) and rabbit anti p-PKA α/β/γ (catalytic subunit) (T197) (1:1000, HuaBio, HA721864, Hangzhou, Zhejiang, China).

Techniques:

Construction of Arrb2 −/− mice and analysis of mRNA and protein levels of downstream candidate genes in the hippocampus. ( A ) Schematic diagram of the construction of Arrb2 −/− mice. ( B ) qRT-PCR analysis of Arrb2 mRNA in the hippocampus of WT and Arrb2 −/− mice. ( C ) Western blot analysis of Arrb2 protein in the hippocampus of WT and Arrb2 −/− mice. ( D – K ) mRNA levels of downstream candidate genes regulated by Arrb2 in the hippocampus of WT and Arrb2 −/− mice measured by qRT-PCR. ( L – O ) Western blot analysis of Myh9, Dnmt1, and Brd4 protein in the hippocampus of WT and Arrb2 −/− mice. ns: p > 0.05, * p < 0.05, *** p < 0.001, unpaired two-tailed Student’s t -test, n = 6 per group.

Journal: Genes

Article Title: Systems Genetics Reveals the Gene Regulatory Mechanisms of Arrb2 in the Development of Autism Spectrum Disorders

doi: 10.3390/genes16050605

Figure Lengend Snippet: Construction of Arrb2 −/− mice and analysis of mRNA and protein levels of downstream candidate genes in the hippocampus. ( A ) Schematic diagram of the construction of Arrb2 −/− mice. ( B ) qRT-PCR analysis of Arrb2 mRNA in the hippocampus of WT and Arrb2 −/− mice. ( C ) Western blot analysis of Arrb2 protein in the hippocampus of WT and Arrb2 −/− mice. ( D – K ) mRNA levels of downstream candidate genes regulated by Arrb2 in the hippocampus of WT and Arrb2 −/− mice measured by qRT-PCR. ( L – O ) Western blot analysis of Myh9, Dnmt1, and Brd4 protein in the hippocampus of WT and Arrb2 −/− mice. ns: p > 0.05, * p < 0.05, *** p < 0.001, unpaired two-tailed Student’s t -test, n = 6 per group.

Article Snippet: The PVDF membrane was incubated at 4 °C overnight with primary antibodies, including mouse anti GAPDH (HRP-conjugated, 1:10,000, Proteintech, 60,004, Wuhan, Hubei, China), rabbit anti β-Arrestin2 (1:1000, Cell Signaling Technology, 3857, Danvers, Massachusetts, USA), rabbit anti Dnmt1 (1:2000, HuaBio, ET1702-77, Hangzhou, Zhejiang, China), rabbit anti Myh9 (1:2000, Abclonal, A0173, Wuhan, Hubei, China), rabbit anti Brd4 (1:1000, HuaBio, HA722785, Hangzhou, Zhejiang, China), rabbit anti p-Synapsin I (S9) (1:1000, HuaBio, ET1611-26, Hangzhou, Zhejiang, China), rabbit anti Synapsin I (1:1000, abcam, ab64581, Cambridge, UK) and rabbit anti p-PKA α/β/γ (catalytic subunit) (T197) (1:1000, HuaBio, HA721864, Hangzhou, Zhejiang, China).

Techniques: Quantitative RT-PCR, Western Blot, Two Tailed Test