Zinc finger protein with KRAB and SCAN domains 1 (ZKSCAN1) (ZKSCAN1)

Zinc finger protein with KRAB and SCAN domains 1 (ZKSCAN1), also widely known as Zinc finger protein 139 (ZNF139), is a member of the Krüppel C2H2-type zinc-finger family of transcription factors [22, 25]. It is characterized by the presence of an N-terminal SCAN domain and a KRAB domain, which facilitate protein-protein interactions and transcriptional repression or activation [1, 4, 13]. ZKSCAN1 plays a critical role in various biological processes, including cell differentiation, proliferation, and the regulation of GABA type-A receptors in the brain [23, 25]. In oncology, it is frequently overexpressed in gastric cancer and hepatocellular carcinoma, where it functions as an oncogenic driver by promoting epithelial-mesenchymal transition (EMT), invasion, and multidrug resistance [1, 4, 6, 23]. It exerts its anti-apoptotic effects by negatively regulating caspase-3 and is itself regulated by microRNAs such as miR-185 and miR-195-5p [1, 4, 23]. Due to its significant correlation with poor prognosis and its role in chemoresistance, ZKSCAN1 is considered a promising therapeutic target for gene-based interventions and a valuable prognostic biomarker in gastrointestinal malignancies [1, 6, 23].

Other names

Zinc finger protein 139ZNF139Zinc finger protein 36ZNF36KOX18Zinc finger protein KOX18ZSCAN33PHZ-37

ZKSCAN1 (ZNF139) acts as a transcriptional regulator that inhibits apoptosis and promotes multidrug resistance. Experimental inhibition via siRNA or microRNA mimics leads to the upregulation of pro-apoptotic factors like caspase-3 and the downregulation of drug efflux transporters such as MDR1 and MRP2, thereby sensitizing cancer cells to chemotherapy.