ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA. It has been linked to regulating histone mRNA polyadenylation-mediated inflammation as a novel RNA binding protein [6]. It was also identified as one of the ATXN1-interacting transcription factors, with altered expression of its target genes observed in SCA1 mice and patient-derived iNeurons [7].

Circular RNA circZKSCAN1 has diverse roles in different cancers. In hepatocellular carcinoma (HCC), a novel polypeptide (circZKSaa) encoded by circZKSCAN1 suppresses HCC via degradation of mTOR, and circZKSCAN1 itself inhibits HCC cell growth, migration, and invasion through different signaling pathways from ZKSCAN1 mRNA [1,5]. In lung adenocarcinoma, circ-ZKSCAN1 promotes tumorigenesis and cisplatin resistance by regulating the miR-185-5p/TAGLN2 axis, while in non-small cell lung cancer, it promotes progression by regulating FAM83A expression and inactivating MAPK signaling via targeting miR-330-5p [2,3]. Conversely, in bladder cancer, circ-ZKSCAN1 inhibits cancer progression through the miR-1178-3p/p21 axis [4].

In conclusion, ZKSCAN1 and its circular RNA form play crucial roles in various biological processes related to cancer and potentially neurodegenerative diseases. Studies on these forms, especially in cancer models, have revealed their significance in tumorigenesis, metastasis, and drug resistance, providing potential therapeutic targets and biomarkers for cancer treatment.