Anti-CDK8 monoclonal antibody, clone 7I6

Up-regulation of long non-coding RNA (lncRNA) XIST has been observed in the tissue samples of non-small cell lung cancer (NSCLC), however, the underlying mechanisms remain uncertain. The aim of this study is to investigate the roles of XIST in the pathogenesis of NSCLC and the underlying mechanism. We noted that XIST in NSCLC tumor tissue and cell lines was significantly up-regulated. XIST over-expression promoted the proliferation and migration, meantime, increased the proportion of cells in the S phase in NSCLC cell line A549 and H1299. Meantime, knockdown of XIST showed the opposite effects. In vivo study further revealed a oncogenic effect of XIST. In addition, we conducted bioinformatics analysis and luciferase activity assay to find out the potential target miR of XIST and the potential target gene of miR-16 which is CDK8. In conclusion, our findings proved that XIST can serve as a tumor promoter in the pathogenesis of NSCLC, suggesting that XIST has the potential to become a novel therapeutic target for the treatment of NSCLC.

A major goal of medicinal chemists is to identify and validate novel and effective kinase targets for treatment of cancer. Recent studies have shown that cyclin-dependent kinase 8 (CDK8) is a target for treatment of colorectal, breast, melanoma, and prostate cancers. The crystal structure of CDK8 has been reported, and eutectic interactions have been identified for 24 compounds that target CDK8. To more effectively develop CDK8 inhibitors, particularly those with improved selectivity, we summarized the structure, structure-activity relationships, and binding information of typical CDK8 inhibitors, which may serve as a reference for development of novel CDK8 inhibitors.