Zkscan1-flox Mouse

ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA [5]. It has been linked to multiple biological processes and disease conditions. ZKSCAN1 has recently been identified as a regulator of histone mRNA polyadenylation-mediated inflammation, acting as a novel RNA binding protein [6]. It has also been found to interact with ATXN1, with altered expression of its target genes observed in SCA1 mice and patient-derived iNeurons, suggesting its potential contribution to spinocerebellar ataxia type 1 pathogenesis [7].

In cancer research, studies on circZKSCAN1, a circular RNA derived from ZKSCAN1, have shown diverse functions. In hepatocellular carcinoma (HCC), circZKSCAN1-encoded peptide circZKSaa suppresses HCC via degradation of mTOR, inhibiting the PI3K/AKT/mTOR pathway, and could be a biomarker and therapeutic target [1]. Additionally, both ZKSCAN1 mRNA and circZKSCAN1 inhibit HCC cell growth, migration, and invasion through different signaling pathways, with ZKSCAN1 mRNA mainly regulating cellular metabolism and circZKSCAN1 mediating cancer-related signaling pathways [5]. In lung adenocarcinoma, circ-ZKSCAN1 promotes tumorigenesis and cisplatin resistance by regulating the miR-185-5p/TAGLN2 axis [2]. In non-small cell lung cancer, circ-ZKSCAN1 promotes progression by acting as a sponge of miR-330-5p to increase FAM83A expression and inactivate the MAPK signaling pathway [3]. Conversely, in bladder cancer, circZKSCAN1 inhibits cancer progression through the miR-1178-3p/p21 axis and can serve as a prognostic factor of recurrence [4].

In conclusion, ZKSCAN1 and its circular RNA counterpart play significant roles in multiple biological processes, especially in cancer and neurodegenerative diseases. Research on ZKSCAN1, particularly through studies on its circular RNA forms in cancer models, has provided insights into disease mechanisms, highlighting its potential as a biomarker and therapeutic target in cancer treatment, and also suggesting its importance in understanding the pathogenesis of spinocerebellar ataxia type 1.