Zinc finger protein 671 has a cancer-inhibiting function in colorectal carcinoma via the deactivation of Notch signaling

Zinc finger protein 671 (ZNF671) has been described as a vital cancer inhibitor in multiple neoplasms, yet the functional roles of ZNF671 in colorectal carcinoma (CRC) remain unresolved. This project examined the possible link between ZNF671 and CRC. Lower levels of ZNF671 were observed in CRC tissue compared with non-cancerous tissue, which were related to a worse survival rate in CRC patients. High methylation levels at the ZNF671 gene promoter region were shown in CRC tissue, which were inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 resulted in suppressive effects on the proliferative ability and metastatic potency of CRC cells. Moreover, the upregulation of ZNF671 reinforced the chemosensitivity of CRC cells. A mechanism study determined ZNF671 to be a vital mediator of Notch signaling. The up-regulation of ZNF671 decreased the expression of Notch1 and lowered the levels of NICD, HES1, and HEY1. The overexpression of NICD1 diminished ZNF671-mediated antitumor effects. ZNF671 depletion reinforced Notch signaling, and Notch suppression reversed ZNF671-depletion-elicited protumor effects. Moreover, the overexpression of ZNF671 weakened the tumorigenicity of CRC cells in a xenograft model in vivo. In summary, ZNF671 exerts a cancer-inhibiting function in CRC via the deactivation of Notch signaling. Low ZNF671 levels caused by gene promoter hypermethylation contribute to the malignant transformation of CRC. This work underlines the interest of ZNF671 as a target candidate for exploiting novel anti-CRC therapies.

Automated summary

Zinc finger protein 671 (ZNF671) is a vital cancer inhibitor in multiple neoplasms, except its roles in colorectal carcinoma (CRC) are still unclear. This study investigated the relationship between ZNF671 and CRC. Low levels of ZNF671 were found in CRC tissue, which correlated with worse survival rate in CRC patients. The ZNF671 gene promoter region in CRC tissue showed high methylation levels, inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 inhibited cell proliferation, metastasis, and enhanced chemosensitivity of CRC cells. Mechanistic study showed ZNF671 as a vital mediator of Notch signaling. In summary, ZNF671 exerts a cancer-inhibiting function in CRC through deactivation of Notch signaling pathway, and can be a potential target for novel anti-CRC therapies.