ZNF714 – a novel oncogene in lung cancer cells

The emerging data indicate that many KRAB-ZNF factors belonging to a large gene family may be involved in carcinogenesis. Our previous study identified ZNF714, a KRAB-ZNF gene of unknown function, as commonly overexpressed in many tumors, pointing to its hypothetical oncogenic role. We knocked down ZNF714 gene expression in two lung cancer cell lines: H2073 (lung adenocarcinoma) and SKMES (squamous cell carcinoma), and subjected them to methylation microarray analysis. We identified 45k DMRs in H2073 and 75k DMRs in SKMES. In both cell lines, the majority of changes (both hypo- and hypermethylation) occurred within gene bodies and promoter regions (TSS1500 and TSS200). The only visible altered methylation pattern indicated more frequent hypomethylation within the promoter region in both shZNF714 cell lines. We correlated those results with our RNA-seq analysis and identified target genes simultaneously overexpressed and unmethylated in cells with knocked-down ZNF714 expression. We identified 54 genes in H2073 and 36 genes in SKMES that met our criteria. Interestingly, several of those genes have documented tumor-suppressive functions, further supporting our in vitro results demonstrating an oncogenic role of ZNF714. We analyzed 6 samples from two different lung cancer cell lines in biological triplicates (total 18 samples). For each cell line (H2073 and SKMES) we analyzed unmodified cells (WT), cells with knocked-down expression of ZNF714 (shZNF714) and cells carrying control shRNA sequence (shLUC).