Fig. 8

CDK7 inhibits c-KIT expression through OSR1 in GIST. A Volcano plot of RNA-seq data displaying the distribution of differential gene expression between THZ1 treatment and DMSO treatment. The upregulated and downregulated genes are highlighted in red and blue, respectively. The results illustrated that OSR1 was the top downregulated gene with the lowest P value. B, C qRT–PCR and immunoblotting analyses showed that OSR1 expression was inhibited by CDK7 knockdown or THZ1 treatment in a dose-dependent manner. OSR1 expression was inhibited by CDK7 knockdown in GIST-T1 and GIST-882 cells. D Gene expression profile in the Oncomine database. The results showed that OSR1 was significantly upregulated in GIST compared with normal gastric tissue. E Gene expression profile in the MediSapiens IST Online transcriptome database. The results showed that OSR1 was uniquely overexpressed in GIST and prostate cancer compared with other cancer types. F Immunoblot analyses of OSR1 expression in clinical sample tissues of GIST, gastrointestinal leiomyoma and schwannoma. The expression of OSR1 was significantly higher in GIST than in leiomyoma and schwannoma. G Data from the MediSapiens database showed that c-KIT and OSR1 expression levels were positively correlated (n = 77, r = 0.407, P < 0.001). H, I qRT–PCR and immunoblotting analyses showed that OSR1 knockdown significantly inhibited c-KIT mRNA and protein expression in GIST-T1 and GIST-882 cells. J Immunoblot analyses showed that OSR1 overexpression promoted c-KIT expression in GIST-T1 and GIST-882 cells. K The inhibitory effect of c-KIT expression was reversed when CDK7 siRNA and OSR1 plasmid were cotransfected into GIST-T1 and GIST-882 cells