ZNF384 mediates KRT23 to promote CRC process through the TGF-β/Smad signaling pathway.

UNLABELLED

Colorectal cancer (CRC) is a common malignancy of the digestive tract and is the second leading cause of cancer-related death worldwide. Keratin 23 (KRT23), a member of the keratin family, is implicated in the development of various cancers. Hence, this study aimed to clarify the molecular mechanism of KRT23 in the progression of CRC. Quantitative real time polymerase chain reaction (qRT-PCR) and western blot were applied to detected RNA and protein levels. Cell migration, invasion, and apoptosis were measured by wound healing, transwell assay, and flow cytometry, respectively. Glycolysis was reflected by the detection of ATP, lactate production, and glucose consumption. What's more, the binding site of zinc finger protein 384 (ZNF384) and KRT23 was predicted using the relevant website and verified by chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assay. Meanwhile, the related proteins were detected by immunohistochemistry (IHC). A mouse xenograft model was established for in vivo analysis and further verified the role of ZNF384 and KRT23 in CRC. KRT23 was highly expressed in CRC tissues and cells. Functionally, silencing KRT23 inhibited CRC migration and invasion, promoted apoptosis, and impeded epithelial-mesenchymal transition (EMT) and glycolysis process by the TGF-β/Smad signaling pathway. In terms of mechanism, ZNF384 bound to the KRT23 promoter, and the inhibition caused by ZNF384 interference was reversed with KRT23. In vivo, knocking down ZNF384 inhibited tumor growth. In summary, ZNF384 could promote the malignant progression of CRC by regulating the KRT23-mediated TGF-β/Smad signaling pathway.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10616-025-00765-z.