ZNF460 inhibits HMGCL and promotes PI3K pathway in colon cancer

Zinc finger protein 460 (ZNF460) is highly expressed in colon cancer, but its specific mechanism of action and downstream targets have not yet been clarified. Therefore, this study aimed to investigate the expression pattern, prognostic value, and biological function of ZNF460 in colorectal cancer (CRC), and to elucidate its underlying molecular mechanisms.

Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, and Western blot assays were used to investigate the biological function of ZNF460 in CRC. Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess ZNF460 expression, prognostic value, and clinical relevance. Functional enrichment, nomogram construction, single-cell sequencing, cell communication, and pseudotime analyses were conducted using R packages including seurat, cluster profiler, cell chat, and monocle 2. Statistical significance was set at P<0.05, with appropriate tests applied based on data type.

ZNF460 expression was upregulated in colon cancer. High expression of ZNF460 was associated with poor clinical stage and prognosis of patients. Cell experiments revealed the role of ZNF460 in promoting colon cancer cell proliferation. Single-cell sequencing revealed that ZNF460 had close interactions with malignant, plasma, endothelial, myofibroblasts and other cells. Bioinformatics analysis and in vitro experiments found that ZNF460 inhibited the expression of hydroxymethyl glutaryl-CoA lyase (HMGCL) and increased the phosphorylation level of phosphatidylinositol-3-kinase (PI3K).

ZNF460 is highly expressed in CRC and is associated with poor prognosis. ZNF460 promotes cancer cell proliferation and participates in tumor cell communication. Mechanistically, ZNF460 activates the PI3K pathway by inhibiting HMGCL expression, thereby promoting the progression of CRC, suggesting that it is a potential therapeutic target.