| 摘要: | Abstract
Hepatocellular carcinoma (HCC), a common malignant tumor, is associated with poor response to cancer therapy. Glucose regulated proteins (GRPs) overexpression is widely reported in cancers, associating with aggressive growth and invasive abilities. The amount of expressed glucose regulated protein 94 (GRP94) is directly correlated with tumor invasiveness in different cancers. However, the role of GRP94 in the HCC progression is not well understood. Here, we investigated the biological role and functions of GRP94 in HCC. We examined the expression level of GRP94 in HCC cell lines and normal liver cells by quantitative polymerase chain reaction (qPCR) and western blotting. We found that GRP94 was highly expressed in the cancer cell lines but not in normal liver cells. To determine the role of GRP94 in HCC progression, the scrambled shRNA and GRP94 shRNA were transfected into HCC cells. The stable scrambled controls and GRP94-KD cells were generated. The proliferation, migration, invasion, and plasmid rescue assays were performed. Our result showed the depletion of GRP94 significantly inhibited cell proliferation, migration and invasion abilities as compared with the scrambled control cells. For mechanism dissection, proliferation and migration related molecules (AKT, ERK, c-Jun, and JNK,etc) were downregulated in GRP94-KD cells. We found that CCT8, subunit of molecular chaperone complex CCT, was down regulated after silencing GRP94. When we overexpressed CCT8, GRP94 expression level was increased. The migration and wound healing assay showed that migratory ability was restored after overexpressing CCT8 in GRP94KD cells. In conclusion, depletion of GRP94 in HCC cell suppressed in vitro proliferation, migration, and invasion capacity by downregulating proliferation and migration related molecules. Overexpression of CCT8 rescued the phenomenon of GRP94-KD cells. Therefore, our study presents that GRP94 plays in vital role in hepatocarcinogenesis and metastasis. |
