Figure 1.

Regulation of ZNF-281 expression and ZNF-281’s role in carcinogenesis. The illustration above shows the most important regulating factors of ZNF-281 expression and outcomes of ZNF-281 stimulation. SOX4 regulates cells’ differentiation and proliferation and induces EMT through ZNF-281. Another pathway stimulating EMT is initiated by Snail. ZNF-281 directly stimulates Snail, creating a positive feedback loop. Any DNA damage, including administering DNA-damaging drugs, will cause an increase in ZNF-281 expression. p53 represses ZNF-281 and its inhibition is mediated by miR34a. ZNF-281 induces epithelial–mesenchymal transition (EMT) and keeps cells in the mesenchymal state, enabling cancerous cells to migrate and invade. Cells acquire a spindle shape, lose E-cadherin in the membrane and have β-catenin translocated from the membrane to the nucleus, resulting in weakening of cell junctions. ZNF-281 induces expression of CD133 and LGR5 (prognostic stem cell markers) and is responsible for cells gaining pluripotency and maintaining their newly acquired stem cell traits. Up-regulated ZNF-281 expression is proven to be correlated with progression and metastasis of the cancers listed above. In glioma, ZNF-281 expression down-regulates NF-κB1 and MMP9 protein expression—both responsible for glioma cells’ invasiveness. In non-small cell lung cancer, ZNF-281 gene expression suppresses carcinogenesis via promotion of apoptosis, inhibition of proliferation and tumor suppression. Therefore, ZNF-281’s down-regulation in glioma and NSCLC is correlated with its progression and metastasis.