Anti-KDM6A (Internal) polyclonal antibody

Epidemiologic data confirmed high-risk human papillomaviruses as etiological agents of cervical cancer. On the other hand genetic and epigenetic modifications are known to play an important role in carcinogenesis. Histone lysine-specific demethylases (KDMs) have been shown to contribute to development and progression of many types of cancer. We evaluated the possible role of KDMs in cervix oncogenesis by analysing their expression in patients with HPV-induced cervical lesions and cancer (86 cervical tissue specimens). HPV DNA was detected and genotyped and KDMs expression levels were investigated by qRT-PCR. Significantly increased genes expression levels of KDM4C, KDM5C, KDM6A and KDM6B were found in CIN2+ lesions and SCC but KDM4C and KDM5C expression levels in SCC samples were significantly higher than in precancerous lesions. A connection between high-risk HPV infection and KDMs in cervical cancer was revealed following experiments using siRNA to silence E6 and E7 oncogenes. Results showed KDMs expression pattern is linked to oncogenic transformation in HPV-induced lesions and could represent new potential diagnostic tools and therapeutic targets in oncology.

The mechanisms of successful epigenetic reprogramming in cancer are not well characterized as they involve coordinated removal of repressive marks and deposition of activating marks by a large number of histone and DNA modification enzymes. Here, we have used a cross-species functional genomic approach to identify conserved genetic interactions to improve therapeutic effect of the histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in more than 20% of patients with advanced acute myeloid leukemia (AML). Using a bidirectional synthetic lethality screen revealing genes that increased or decreased VPA sensitivity in C. elegans, we identified novel conserved sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which demonstrates a functional relationship between protein acetylation and lysine-specific methylation. The synthetic lethal screen identified resistance programs that compensated for the HDACi-induced global hyper-acetylation, and confirmed MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs represent promising novel targets for refinement of combinatorial epigenetic anti-cancer therapy.