TY - JOUR
T1 - Action and clinical significance of CCAAT/enhancer-binding protein delta in hepatocellular carcinoma
AU - Liu, Pengyu
AU - Cao, Wanlu
AU - Ma, Buyun
AU - Li, Meng
AU - Chen, Kan
AU - Sideras, Kostandinos
AU - Duitman, Jan-Willem
AU - Sprengers, Dave
AU - Khe Tran, T. C.
AU - Ijzermans, Jan N. M.
AU - Biermann, Katharina
AU - Verheij, Joanne
AU - Arnold Spek, C.
AU - Kwekkeboom, Jaap
AU - Pan, Qiuwei
AU - Peppelenbosch, Maikel P.
PY - 2019/3/12
Y1 - 2019/3/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062856037&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30325409
U2 - https://doi.org/10.1093/carcin/bgy130
DO - https://doi.org/10.1093/carcin/bgy130
M3 - Article
C2 - 30325409
SN - 0143-3334
VL - 40
SP - 155
EP - 163
JO - Carcinogenesis
JF - Carcinogenesis
IS - 1
ER -