ZNF251 is a novel prognostic biomarker and correlated with the immunosuppressive microenvironment in hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) persists as the most common malignant tumor worldwide. Therefore, it is crucial to investigate its pathogenic mechanism and explore its potential prognostic and therapeutic targets However, the role of zinc finger protein (ZNF)251 in HCC is unclear. Methods The Cancer Genome Atlas (TCGA)-HCC transcriptional profiles were used to investigate the ZNF251 expression in HCC and normal samples and explore the effect of ZNF251 on HCC prognosis. ZNF251 expression and its role in pan-cancer were examined via several other databases ZNF251 mRNA and protein expression levels in clinical HCC tissues and cell lines were measured by RT-qPCR and western blotting, respectively. Following small interfering RNA (siRNA)-mediated ZNF251 knockdown, the effects of ZNF251 on HCC cell proliferation, migration, and invasion were evaluated in vitro experiments. The effect of ZNF251 on HCC growth in vivo was investigated via a nude mouse subcutaneous model. Furthermore, the effect of ZNF251 on infiltrating immune cells and the associations between ZNF251 and the genes of interest were analyzed with TIMER2 and GEPIA2. Finally, the relationship between ZNF251 and chemokines was investigated via TISIDB. Results ZNF251 was highly expressed in HCC, and promoted HCC cell proliferation, migration, and invasion by activating the extracellular-regulated protein kinase (ERK) signaling pathway. ZNF251 was associated with poor prognosis of HCC and was highly expressed in most cancers. Further analyses revealed that ZNF251 was positively associated with regulatory T cell (Treg) infiltration and Treg-related immunosuppressive cytokine expression. Moreover, ZNF251 was tightly related to the expression of classic exhaustion markers of CD8+ T cells. ZNF251 significantly affected the expression of 10 chemokines in HCC (CCL2, CCL4, CCL5, CCL11, CCL13, CCL14, CCL23, XCL2, CXCL17, CCL20), which indicated that ZNF251 might affect HCC immune profiles by regulating chemokine expression. Conclusion ZNF251 functions as an oncogene in HCC and can serve as a new prognostic biomarker and therapeutic target.