SKIL, also known as ski-related novel gene (SnoN), is a transcription co-factor. It is involved in regulating multiple biological processes, especially in the context of the TGF-β signaling pathway where it acts as a negative regulator [2,5]. This regulation has implications for cell proliferation, apoptosis, differentiation, and senescence, making it important in normal development and disease [4]. Gene knockout mouse models can be valuable in understanding the specific functions of SKIL in vivo.

In colorectal cancer, Nsun2 knockout mouse models showed that NSUN2 promotes cancer progression by enhancing SKIL mRNA stabilization. NSUN2-induced m5C modification of SKIL and its stabilization via YBX1 led to increased TAZ activation, driving cancer growth [1].

In hepatic fibrosis, SKIL/SnoN expression was downregulated in fibrotic livers. Overexpression of SnoN in HSC-T6 and LX-2 cell lines promoted apoptosis and reduced the expression of fibrosis-associated proteins, while down-regulation of SnoN had the opposite effect, suggesting its role in attenuating TGF-β1/SMADs signaling-dependent collagen synthesis [2].

In NSCLC, silencing of SKIL in cell lines and xenograft mouse models inhibited malignant phenotypes and promoted T cell infiltration, indicating its role in promoting tumorigenesis and immune escape through upregulating the TAZ/autophagy axis [3].

In conclusion, SKIL is a key regulator in the TGF-β signaling pathway with functions in multiple biological processes. Model-based research, especially using gene knockout mouse models, has revealed its significance in diseases such as colorectal cancer, hepatic fibrosis, and NSCLC. Understanding SKIL's functions provides potential therapeutic targets for these diseases.