Fig 1: Schematic representation of the study.Briefly, in LUAD, YAP m5C modification on its 3'UTR depends on NSUN2 and ALYREF, and this m5C modification inhibits its m6A modification and miR-582-3p binding. Furthermore, YAP m5C modification increases YAP mRNA stability and stimulates Mycn- and SOX10-dependent exosome secretion-related genes including HRS, PLD2, RAB2B, RAB27A, RAB27B, VAMP and ATG7.
Fig 2: YAP stimulates transcription of exosome secretion genes via Mycn and SOX10.A Genes related to exosome biogenesis, transport and release were listed. B Indicated mRNA levels were measured by qPCR in YAP overexpressed or knocked out A549 cells. C Mycn, SOX10 and SPI1 binding motif found from JASPAR database. D, E Exosome concentration (D) and HRS, PLD2, RAB2B, RAB27A, RAB27B, VAMP and ATG7 mRNA levels (E) in A549 cells with Mycn, SOX10 or SPI1 overexpressed. F, G Exosome concentration (F) and HRS, PLD2, RAB2B, RAB27A, RAB27B, VAMP and ATG7 protein levels (G) in A549 cells with YAP overexpressed with or without Mycn or SOX10 knockout. The level of proteins was normalized to that of GAPDH, and the normalized level of proteins in negative control groups were arbitrarily set to 1. H, I Exosome concentration (H) and HRS, PLD2, RAB2B, RAB27A, RAB27B, VAMP and ATG7 protein levels (I) in A549 cells with indicated genes overexpressed or knocked out. The level of proteins was normalized to that of GAPDH, and the normalized level of proteins in negative control groups were arbitrarily set to 1. The data are shown as the means ± SD from three independent experiments. Images of IB are representative ones of three independent experiments. *p < 0.05, **p < 0.01 indicate statistical significance. The data from (B) were analyzed by a student’s t test. The data from (D–F, H) were analyzed by a one-way ANOVA test.
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