Zcrb1, also known as zinc finger CCHC-type and RNA-binding motif 1 (alias MADP-1), is a core component of the U12 mono-snRNP minor spliceosome. It plays a crucial role in regulating the splicing and expression of U12-type genes, and is involved in important biological processes such as ciliogenesis and the WNT signaling pathway. Its function is evolutionarily conserved across species, highlighting its overall biological importance [1,3].

In human cell lines, partial reduction of ZCRB1 expression via CRISPR-Cas9 and siRNA strategies led to significant dysregulation of U12-type gene splicing and expression, mainly due to U12 mono-snRNA dysregulation. This further resulted in downregulation of ciliogenesis-related genes and upregulation of WNT signaling. In zebrafish embryos, zcrb1 CRISPR-Cas12a knockdown caused gross developmental and body axis abnormalities, disrupted ciliogenesis, and upregulated WNT signaling, complementing the human cell studies [1]. In glioblastoma multiforme (GBM) cells, overexpression of ZCRB1 promoted the formation of circHEATR5B, which in turn suppressed aerobic glycolysis and proliferation in GBM cells through a novel pathway involving phosphorylation of JMJD5 [2]. In head and neck squamous cell carcinoma (HNSCC), knockdown of ZCRB1 impaired cell survival, while overexpression promoted tumor cellular proliferation, and its depletion contributed to aberrant splicing events in DNA damage response [4].

In conclusion, Zcrb1 is essential for the regulation of splicing, ciliogenesis, and WNT signaling. Model-based research, such as gene knockdown in human cell lines and zebrafish embryos, has revealed its significant roles in these biological processes. In diseases like GBM and HNSCC, Zcrb1 also shows potential as a therapeutic target, with its manipulation affecting key aspects of tumor cell behavior.