Journal: Oncotarget

Article Title: MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma

doi: 10.18632/oncotarget.8916

Figure Lengend Snippet: Empty plasmid- and MIR126 -transfected H28 cells, and their IRS1-silenced (IRS1-) or IRS1-overexpressing (IRS1+) counterparts were analyzed for AV formation A. IRS1 levels and LC3 conversion B. Densitometric analysis of IRS1 and LC3 conversion related to actin (right panel). Scale bar for all images equals 10 μm. The data shown are mean values ± S.D. derived from three independent experiments. Comparisons among groups were determined by one-way ANOVA with Tukey post-hoc analysis; the symbol “*” indicates significantly different values compared with scramble control with p < 0.05.

Article Snippet: Anti-IRS1 sequence 5′-AGA CCA UCA GCU UCG UGA ATT-3′ (Ambion), or human IRS1 plasmid (SC124032, OriGene), were used to transiently silence or overexpress IRS1, respectively.

Techniques: Plasmid Preparation, Transfection, Derivative Assay, Control

Journal: Oncotarget

Article Title: MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma

doi: 10.18632/oncotarget.8916

Figure Lengend Snippet: MIR126 targets the expression of IRS1 resulting in the insulin signaling pathway disruption. This contributes to lower glucose uptake. Upon energy depletion, the AMPK pathway is activated and induces lysosomal autophagy. Inhibition of ACL by MIR126 contributes to citrate accumulation in cytosol, inducing HIF1α activation and stabilization, leading to GLUT-4 upregulation. MIR126 induces PDK down-regulation, which in conjunction with ACL inhibition paradoxically inhibits PDH, possibly due to the high level of NADH and citrate/pyruvate in mitochondrial matrix. The associated HIF1α stabilization results in lipid droplets accumulation (LD) via increased ‘glyceroneogenesis’ . This complex metabolic program leads to the loss of malignancy in MM. The activated pathways are shown in red. OAA, oxaloacetic acid; Mal, malic acid; PEP, phosphoenolpyruvate.

Article Snippet: Anti-IRS1 sequence 5′-AGA CCA UCA GCU UCG UGA ATT-3′ (Ambion), or human IRS1 plasmid (SC124032, OriGene), were used to transiently silence or overexpress IRS1, respectively.

Techniques: Expressing, Disruption, Inhibition, Activation Assay