Action and clinical significance of CCAAT/enhancer-binding protein delta in hepatocellular carcinoma

作者：Liu, Pengyu; Cao, Wanlu; Ma, Buyun; Li, Meng; Chen, Kan; Sideras, Kostandinos; Duitman, Jan-Willem; Sprengers, Dave; Tran, T. C. Khe; Ijzermans, Jan N. M.; Biermann, Katharina; Verheij, Joanne; Spek, C. Arnold; Kwekkeboom, Jaap; Pan, Qiuwei; Peppelenbosch, Maikel P.^*

来源：Carcinogenesis, 2019, 40(1): 155-163.

DOI：10.1093/carcin/bgy130

• C/EBP-DELTA
• TUMOR MICROENVIRONMENT
• BREAST-CANCER
• EXPRESSION
• CELLS
• SUPPRESSOR
• GROWTH
• BETA

We demonstrate that candidate tumor suppressor gene CEBPD downregulation provokes poor prognosis of clinical HCC. Remarkably, CEBPD drives HCC compartment expansion in experimental HCC. Interaction of CEBPD with interleukin signaling may explain this discrepancy.
Abstract CCAAT/enhancer-binding protein delta (CEBPD) is associated with the regulation of apoptosis and cell proliferation and is a candidate tumor suppressor gene. Here, we investigated its role in hepatocellular carcinoma (HCC). We observe that CEBPD mRNA expression is significantly downregulated in HCC tumors as compared with adjacent tissues. Protein levels of CEBPD are also lower in tumors relative to adjacent tissues. Reduced expression of CEBPD in the tumor correlates with worse clinical outcome. In both Huh7 and HepG2 cells, shRNA-mediated CEBPD knockdown significantly reduces cell proliferation, single cell colony formation and arrests cells in the G(0)/G(1) phase. Subcutaneous xenografting of Huh7 in nude mice show that CEBPD knockdown results in smaller tumors. Gene expression analysis shows that CEBPD modulates interleukin-1 signaling. We conclude that CEBPD expression uncouples cancer compartment expansion and clinical outcome in HCC, potentially by modulating interleukin-1 signaling. Thus, although our results support the notion that CEBPD acts as a tumor suppressor in HCC, its action does not involve impairing compartment expansion per se but more likely acts through improving anticancer immunity.

• 出版日期2019-1
• 单位浙江理工大学